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Cellular uptake, genotoxicity and cytotoxicity of Cobalt Ferrite Magnetic Nanoparticles in human breast cells
Abstract
Magnetic nanoparticles (MNPs) have been increasingly used for many years as MRI agents and for gene delivery and hyperthermia therapy, although there have been conflicting results on their safety. In this study, cobalt ferrite magnetic nanoparticles (CoFe-MNPs) were prepared by the co-precipitation method and their surfaces were modified with silica by the sol-gel method. The particle and hydrodynamic sizes, morphology and crystal structure of the bare and silica-coated CoFe-MNPs were evaluated by transmission electron microscopy (TEM), dynamic light scattering (DLS), X-ray diffraction spectroscopy (XRD) and Fourier transform infrared spectroscopy (FTIR). The size of the bare CoFe-MNPs was in the range 8-20 nm and they were homogeneously coated with 3-4 nm silica shells. The bare and silica-coated CoFe-MNPs were agglomerated at physiological pH. However, the sizes of the agglomerates were below 200 nm both in water and complete medium. The cytotoxic and genotoxic potentials of the bare and silica-coated CoFe-MNPs were evaluated in a metastatic breast cancer cell line, MDA-MB-231, as well as a noncancerous mammary epithelial cell line, MCF-10A, by using XTT cytotoxicity, single-cell gel electrophoresis (comet), and cytokinesis-blocked (CB) micronucleus (CBMN) assays. Characterization studies with TEM, inductively coupled plasma optical emission spectroscopy (ICP-OES) and Prussian blue staining indicated that the CoFe-MNPs were internalized into the cells by energy-dependent endocytosis. The highest amount of uptake was observed in the cancer cells and the uptake of the silica-coated CoFe-MNPs was higher than that of the bare ones in both cell lines. The bare CoFe-MNPs showed higher levels of both cytotoxicity and genotoxicity than the silica-coated CoFe-MNPs. Moreover, the cancer cells seemed to be more susceptible to the CoFe-MNPs' toxicity compared to the noncancerous cells. There was a concentration and time-dependent increase in DNA damage and the micronucleus (MN) frequency, which was statistically significant starting with the lowest concentration of bare CoFe-MNPs (p < 0.05), while no significance was observed below the concentration of 250 μg mL⁻¹ for the silica-coated MNPs. Also, the extent of both DNA damage and MN frequency was much higher in the cancer cells compared to the noncancerous cells. According to our results, the silica coating ameliorated both the cytotoxicity and genotoxicity as well the internalization of the CoFe-MNPs.
... The MNPs colloidal suspension was used for silica coating using sol-gel method [21]. After silica coating process, the nanoparticle (NP) surface was modified with amine groups using APTES (3-aminopropyl trimethoxysilane; Sigma-Aldrich) and functionalized with -COOH by using glutamic anhydride (Sigma-Aldrich; COOH-MNPs) [22,23]. For the characterization of COOH-functionalized MNPs, dynamic light scattering (DLS) and Fourier transform infrared (FT-IR) spectroscopy methods were utilized. ...
... We have previously demonstrated that coating of CoFe-NPs with silica enhances the uptake and internalization of MNPs into breast cancer cells [23]. We also found that the uptake of the silica-coated and bare CoFe-MNPs were significantly reduced by 45% in the MDA-MB-231 cell line when cells are treated with metabolic inhibitors [23], suggesting that metabolic activity contributes to the uptake. ...
... We have previously demonstrated that coating of CoFe-NPs with silica enhances the uptake and internalization of MNPs into breast cancer cells [23]. We also found that the uptake of the silica-coated and bare CoFe-MNPs were significantly reduced by 45% in the MDA-MB-231 cell line when cells are treated with metabolic inhibitors [23], suggesting that metabolic activity contributes to the uptake. In addition, ζ potential of MNPs in the presence of proteins under physiological conditions decrease. ...
Aim: To investigate the role of EF2K in BRCA1-mutated breast cancer. Materials & methods: We developed silica coated cobalt-ferrite (CoFe) nanoparticles for in vivo delivery of small interfering RNAs (siRNAs) into BRCA1-mutated breast cancer. Results: Expression of EF2K is highly upregulated in the majority (78.5%) of BRCA1-mutated patients and significantly associated with poor patient survival and metastasis. Silencing of EF2K reduced cell proliferation, migration and invasion of the cancer cells. In vivo therapeutic targeting of EF2K by CoFe-siRNA-nanoparticles leads to sustained EF2K gene knockdown and suppressed tumor growth in orthotopic xenograft models of BRCA1-mutated breast cancer. Conclusion: EF2K is a potential novel molecular target in BRCA1-mutated tumors and CoFe-based siRNA nanotherapy may be used as a novel approach to target EF2K.
... Therefore, the mechanism of the NPs' entrance into cells may be different in different cells. Also, cancer cells have a higher capacity for endocytosis due to their high metabolic activity compared to normal cells [49]. The internalization of NPs into cells plays a major role in causing cytotoxicity and therefore irreversible damages [17,18]. ...
... The internalization of NPs into cells plays a major role in causing cytotoxicity and therefore irreversible damages [17,18]. The internalization potential of GNPs into a cell depends on several factors [48] including the GNPs' size, shape (morphology), surface modification, concentration, the time duration that GNPs are exposed to the cancer cells as well as cell type and ligand type [17,39,[49][50][51]. The NPs' size is an important factor which affects on their cellular uptake, intracellular distribution, and cytotoxicity [52]. ...
... The NPs' size is an important factor which affects on their cellular uptake, intracellular distribution, and cytotoxicity [52]. Also, it has been shown that cellular responses to PTT depend on the size of NPs; a comparison between different sizes of the spherical GNPs has revealed that the size of 50 nm has the greatest efficiency in entering into the cell [17,49]. Different shapes of NPs show the different level of interaction with the cells' membrane and consequently a different cellular uptake occurs [18]. ...
Hyperthermia is an anti-cancer treatment in which the temperature of the malignant tumor is increased more than other adjacent normal tissues. Microwave, ultrasound, laser, and radiofrequency sources have been used for hyperthermia of cancerous tissues. In the past decade, near-infrared (NIR) laser for cancer therapy, known as photo-thermal therapy (PTT), was expanded in which the photo-sensitizer agent converts the light photon energy to heat. The heat following PTT can destroy cancer cells. There are some photo-sensitizer agents which have been used for PTT; however, owing to recent advances in nanotechnology, noble metal nanoparticles like gold (Au) nanoparticles (GNPs) have been used successfully in PTT. GNPs have some desirable specifications, including simple and controlled synthesis, small size, high level of biocompatibility, and surface plasmon resonance (SPR). The SPR effect of the GNPs increases the radiative properties like absorption and scattering; therefore, they can be used in PTT. In this article, we reviewed recent in vitro studies of PTT using GNPs in literature. At first, we focus on the physical properties of GNPs, their interaction with infrared radiation, and physical parameters governing the interaction of infrared radiation with the GNPs. Then, we review the passive and active targeting of GNPs using the different coating to induce the thermal damage in cancer cells using low-level laser PPT. The GNPs’ cellular internalization into cancer cells is a challenge which is consequently considered. In this review, we also summarize the results of synergistic cancer therapy studies on the combination of radiation therapy as a routine cancer treatment and PTT: in which significant improvement occurs in treatment efficacy.
... From the literature, CoFe 2 O 4 nanoparticles and MoS 2 nanosheets have also been found to have profound cytotoxic effects and to increase the cell viability of various cancer cells [14][15][16][17]. These two members were promising anticancer agents, which increased interest in hybridizing these two materials to enhance the anticancer property with biocompatibility [15,[18][19][20]. ...
... From the literature, CoFe 2 O 4 nanoparticles and MoS 2 nanosheets have also been found to have profound cytotoxic effects and to increase the cell viability of various cancer cells [14][15][16][17]. These two members were promising anticancer agents, which increased interest in hybridizing these two materials to enhance the anticancer property with biocompatibility [15,[18][19][20]. Although the cost-effective fabrication of dichalcogenide materials for cancer therapies remains a huge challenge, inspired by the above needs, a facile design that improves many functionalities into a single nano platform based on superparamagnetic CoFe 2 O 4 and MoS 2 nanosheets is a promising dichalcogenide material for future food and biomedical applications. ...
In this work, the fabrication of CoFe2O4 nanodots–MoS2 nanosheets with double PEGylation (COMPI) is achieved by cost-effective methods. The preparation techniques were preferred to cost-effectively enhance the properties and biocompatibility of cobalt ferrite and dichalcogenide nanomaterials. Structural and morphological investigations were done using powder XRD, TEM, XPS, and FT-IR techniques. CoFe2O4 nanodots exhibit superparamagnetic behaviour, and the magnetization decreases with the addition of MoS2 nanosheets and when double-coated with PEG-non-ionic surfactants. This material was designed to study anticancer, antioxidant, and antimicrobial efficacy. The anticancer activity of COMPI in MCF-7 adenocarcinoma (breast cancer) and HepG-2 hepatocellular carcinoma (liver cancer) cell lines was evaluated. A strong cytotoxic potential was observed for both MCF-7 and HepG-2 cell lines and negligible hemolytic activity. Antioxidant assay of SOD and H2O2 were assessed as toxicity end-points. Antimicrobial properties against Staphylococcus aureus, Escherichia coli, and Candida albicans showed noteworthy results. This study shows a key to understanding the ferrite nanodots encased in 2D MoS2 nanosheets with PEGylation forming a unique interaction and the strategy for obtaining in vitro efficiency, which provides strong evidence to support the development of cytotoxicity antioxidant, and antimicrobial properties for significant biomedical potential in nanotherapy.
... As a result, the mechanism by which NPs enter cells may differ between cells. Furthermore, cancer cells have a greater capacity for endocytosis than normal cells due to their high metabolic activity [130]. NPs internalization into cells is a major contributor to cytotoxicity and thus irreversible damage [43]. ...
... The NPs size influences their cytotoxicity, intracellular distribution, and cellular uptake [131]. Besides, it has been demonstrated that the cellular responses to PTT are dependent on NPs size; an evaluation of various sizes of spherical AuNPs confirmed that 50 nm has the highest advantage in entering the cell [130]. Various NP shapes exhibit varying degrees of interaction with the membrane of cells, resulting in varying cellular uptake. ...
AuNPs-mediated photothermal therapy (PTT) is gaining popularity in both laboratory research and medical applications. It has proven clear advantages in breast cancer therapy over conventional thermal ablation because of its easily-tuned features of irradiation light with inside hyperthermia ability. Notwithstanding this significant progress, the therapeutic potential of AuNPs-mediated PTT in cancer treatments is still impeded by several challenges, including inherent non-specificity, low photothermal conversion effectiveness, and the limitation of excitation light tissue penetration. Given the rapid progress of AuNPs-mediated PTT, we present a comprehensive overview of significant breakthroughs in the recent advancements of AuNPs for PTT, focusing on breast cancer cells. With the improvement of chemical synthesis technology, AuNPs of various sizes and shapes with desired properties can be synthesized, allowing breast cancer targeting and treatment. In this study, we summarized the different sizes and features of four major types of AuNPs in this review: Au nanospheres, Au nanocages, Au nanoshells, and Au nanorods, and explored their benefits and drawbacks in PTT. We also discussed the diagnostic, bioconjugation, targeting, and cellular uptake of AuNPs, which could improve the performance of AuNP-based PTT. Besides that, potential challenges and future developments of AuNP-mediated PTT for clinical applications are discussed. AuNP-mediated PTT is expected to become a highly promising avenue in cancer treatment in the near future.
... These DNA lesions can lead to gene mutations, chromosomal aberrations, apoptosis, carcinogenesis or cellular senescence if left unrepaired [53]. A wealth of evidence supports the idea of a potential genotoxic risk associated to many different NPs [8,46,[54][55][56]. (e) Other negative physiological effects that can partially or completely impair normal cell and organ functioning have been reported for NPs in the nanomedicine field [9,45,57]. ...
... DiIC1 (5) [56]. As it can be seen in Table 1, no clear trend between Co-FNP size or synthesis method and cytotoxicity can be deduced. ...
In the last years, nanoferrites have gained much attention in the fields of bio- and nanomedicine due to their diverse potential applications in magnetic hyperthermia and targeted drug delivery for cancer treatment, as well as contrast agents for magnetic resonance imaging, among others. These materials are relatively easy to synthesize at low cost and present good physical and chemical stability. Most importantly, their magnetic properties can be precisely tuned by varying the nature and content of the divalent co-ion (e.g. Co²⁺, Ni²⁺, Mn²⁺, etc.) or co-ions in mixed ferrites. In this context, evaluating their toxicity and biocompatibility is mandatory prior to their application in pharmaceutical products. In this chapter, we summarize the state-of-the-art of nanoferrites’ toxicity evaluation, both in vitro and in vivo.
... To facilitate the detection of spatial distribution of tumor associated macrophages (TAMs), and to allow the quantification of deposited iron, it is possible to collect a T2* map with a multi-gradient echo sequence; an alternative is to quantify the change in susceptibility caused by the contrast agent via quantitative susceptibility mapping. Both these methods are linearly related to the concentration of iron oxide NPs [25,26]. This review will be mainly focused on studies of tumor immunotherapy, which we see as a relevant application in the near future. ...
... To facilitate the detection of spatial distribution of tumor associated macrophages (TAMs), and to allow the quantification of deposited iron, it is possible to collect a T2 * map with a multi-gradient echo sequence; an alternative is to quantify the change in susceptibility caused by the contrast agent via quantitative susceptibility mapping. Both these methods are linearly related to the concentration of iron oxide NPs [25,26]. This review will be mainly focused on studies of tumor immunotherapy, which we see as a relevant application in the near future. ...
Starting from the mid-1990s, several iron oxide nanoparticles (NPs) were developed as MRI contrast agents. Since their sizes fall in the tenths of a nanometer range, after i.v. injection these NPs are preferentially captured by the reticuloendothelial system of the liver. They have therefore been proposed as liver-specific contrast agents. Even though their unfavorable cost/benefit ratio has led to their withdrawal from the market, innovative applications have recently prompted a renewal of interest in these NPs. One important and innovative application is as diagnostic agents in cancer immunotherapy, thanks to their ability to track tumor-associated macrophages (TAMs) in vivo. It is worth noting that iron oxide NPs may also have a therapeutic role, given their ability to alter macrophage polarization. This review is devoted to the most recent advances in applications of iron oxide NPs in tumor diagnosis and therapy. The intrinsic therapeutic effect of these NPs on tumor growth, their capability to alter macrophage polarization and their diagnostic potential are examined. Innovative strategies for NP-based drug delivery in tumors (e.g., magnetic resonance targeting) will also be described. Finally, the review looks at their role as tracers for innovative, and very promising, imaging techniques (magnetic particle imaging-MPI).
... Perfluorocarbon nanoemulsions (PFC) and 19F MRI were used by Weibel and colleagues [26] to establish a longitudinal, noninvasive monitoring of intratumoral inflammation during oncolytic virotherapy. By comparing in vivo and ex vivo 19F/1H MRI with histology, the authors demonstrated the potential of this imaging modality for the localization of the host immune response and for sentinel lymph node detection. ...
Iron oxide nanoparticles have been used in medicine for around 90 years, and this time has demonstrated their versatility, therapeutic efficacy, and safety. The primary constituents of iron oxide nanoparticles (IONs) are either magnetite (FeO Fe2O3) or maghemite (-Fe2O3). The most major clinical application of IONs is based on MRI. To detect cancers and age-related diseases, IONs are being used in medical diagnostic imaging. The two IONs with the best clinical repute are Resovist and Feridex IV. In addition to being used to detect cancers, IONs are also adapted as gastrointestinal negative contrast agents and as slow-release iron supplements to treat iron deficiency anemia. With IONs exposed to alternating magnetic fields, targeted imaging and thermal energy production are both feasible. Radiation therapy, immunotherapy, or chemotherapy be facilitated by the effects of heat. A growing number of IONs are being studied in therapeutic settings as nanotechnology develops swiftly. How IONs are used in biomedicine is determined by their interaction with the human immune system.
... Demirci Due to the wide range of industrial application of the ferrites as well as their high availability in the environment, the cells of human body are constantly exposed to their 6 harmful effects [35]. The different ways of their administration to human body and their easy uptake by cells result in the altered metabolism, decreased viability and increased oxidative stress [35][36][37][38]. Cobalt ferrite NPs have been previously shown to affect the viability and redox homeostasis of different cells [39,40]. ...
Bulk and nanostructurized lanthanum-cobalt spinels have attracted a lot of interest from researchers, due to their unique physical and chemical properties as well as functionalities, which are interesting for biomedical and electronic industries. In this manuscript we show that introducing small lanthanum (La3+) content can tune magnetic, electronic and cytotoxic properties of the CoFe2-xLaxO4 system (x ≤0.1). The mechanisms of the tuning are comprehensively studied by theoretical electronic structure calculations; spectroscopic methods (FTIR, Mossbauer, XAS); structural and microstructural research; magnetometry; and cytotoxic viabilities of normal and cancer cells. It was found that the mechanism originate mainly from the complex exchange inter
action of the 3d states of cations with 2p states of oxygen caused by mixing of the metals over the tetragonal and octahedral positions. For synthesized CoFe2-xLaxO4 nanoparticles (NPs) in vitro studies of toxicity on the tested cell lines (human Hs27 fibroblasts, A375 melanoma, Nthy-ori 3-1 thyrocytes, and FTC-133 thyroid cancer cells) revealed that CoFe2-xLaxO4 NPs have high impact on cancer cells, while their toxicity towards normal cells is significantly lower. Along to soft magnetic properties this is a key factor for functionalization.
... For example, the use of NPs of zinc-doped cobalt ferrite (CFO_Zn) makes it possible to increase the magnetic anisotropy [12,13]. Also, CFO NPs have a weak cytotoxic effect, provided that they are synthesized with a biocompatible coating and used at low concentrations [14][15][16]. ...
The rapid development of the nanomaterials’ application’s fields in biomedicine is associated with the expanded possibilities of combining their properties in composite materials. The use of nanocomposites allows application in various types of therapy or theranostics. In this work, we propose a new approach for the fabrication of a gold/ferrite nanocomposite, which consists of gold particles up to 10 nm in diameter surrounded by small nanoparticles of cobalt ferrite (~5 nm) doped with zinc. The gold core is coated with arginine, while the ferrite particles have dihydrocaffeic acid shell. The fabricated nanocomposite possesses optical and magnetic properties due to the excitation of localized plasmon resonance in gold particles and the superparamagnetic state of ferrite particles. The results of studying the structural, magnetic, and optical properties, as well as the cytotoxicity of the obtained nanocomposite, allow us to conclude that it can be used in combined photo- and magnetic hyperthermic therapy.
... It belongs to a family of M 2+ Fe 3+ 2 O 4 -type spinel ferrites (where M 2+ is a divalent metal). The CFO nanoparticles have a moderate cytotoxicity effect on human cells if loaded into biocompatible coatings and used in proper concentrations [6][7][8]. Jurkat cells also show low short-term toxicity on CFO nanoparticles covered in silica [9]. It was also shown, that in low concentrations CFO nanoparticles without any covering with diameters below 10 nm show almost no inhibition of cell proliferation or general toxic effects, still accumulating in cells intracellularly and perinuclearly [10]. ...
The combination of plasmonic material and magnetic metal oxide nanoparticles is widely used in multifunctional nanosystems. Here we propose a method for the fabrication of a gold/cobalt ferrite nanocomposite for biomedical applications. The composite includes gold cores of ~10 nm in diameter coated with arginine, which are surrounded by small cobalt ferrite nanoparticles with diameters of ~5 nm covered with dihydrocaffeic acid. The structure and elemental composition, morphology and dimensions, magnetic and optical properties, and biocompatibility of new nanocomposite were studied. The magnetic properties of the composite are mostly determined by the superparamagnetic state of cobalt ferrite nanoparticles, and optical properties are influenced by the localized plasmon resonance in gold nanoparticles. The cytotoxicity of gold/cobalt ferrite nanocomposite was tested using T-lymphoblastic leukemia and peripheral blood mononuclear cells. Studied composite has selective citotoxic effect on cancerous cells while it has no cytotoxic effect on healtly cells. The results suggest that this material can be explored in the future for combined photothermal treatment and magnetic theranostic.
... Present results confirm the biocompatibility of the studied NPs up to 250 μg.ml -1 in agreement with other investigations [50,51]. Different biocompatibility of ferrite NPs has been reported in the literature and ascribed to high biological reactivity, being influenced by NP parameters such as size, size distribution, crystallinity, shape and surface charge, and also biological aspects such as cell line, medium composition, exposure conditions and cell viability assay [52][53][54][55]. ...
Aim: Evaluation of the biocompatibility and radiosensitizer potential of citrate-coated cobalt (cit-CF) and nickel (cit-NF) ferrite nanoparticles (NPs). Materials & methods: Normal fibroblast and breast cancer cells were treated with different concentrations of citrate-coated ferrite NPs (cit-NPs) and irradiated with a cobalt-60 source at doses of 1 and 3 Gy. After 24 h, cell metabolism, morphology alterations and nanoparticle uptake were evaluated. Results: Cit-CF and cit-NF NPs showed no toxicity to normal cells up to 250 and 100 μg.ml ⁻¹ , respectively. Combination of cit-NP and ionizing radiation resulted in up to fivefold increase in the radiation therapeutic efficacy against breast cancer cells. Conclusion: Cit-CF and cit-NF NPs are suitable candidates for application as breast cancer cell radiosensitizers.
... Cobalt ferrite nanoparticles (CoFe2O4 NPs) have attracted a great interest for medical application over recent years, because they present useful properties such as thermal stability, mechanical hardness, high magnetocrystalline anisotropy (180 -200 kJ•m -3 ) compared to Fe3O4 and larger coercivity combined with a moderate Ms (50 -90 Am 2 /kg) [1], [2]; even though some researchers have raised the toxicity issue [3][4][5]. These characteristics make CoFe2O4 NPs candidate materials for use in a wide range of applications (e.g. ...
Cobalt ferrite nanoparticles (NPs) doped with rare earth (RE) metals with general formula CoFe2-xRExO4 (RE=Yb, Dy, Gd; x = 0.0 - 0.3) were synthesized by the co-precipitation method followed by post thermal treatment. The influence of RE doping on structural, magnetic and thermal properties and potential biomedical applications like magnetic hyperthermia has been investigated. In the as-prepared samples RE cations enter the spinel lattice as detected by X-ray diffraction. Thermal treatment leads to thermodynamically stable and relaxed single-phase spinel structures only for lower RE content, x = 0.01-0.05. However, annealed samples present higher mass magnetization values (MS), up to 83 Am2/kg. RE content also affects MS, especially in the case of annealed samples where it decreases linearly with x from about 80 Am2/kg (x = 0.01) to about 60 Am2/kg (x = 0.30). Thermal treatment induces a reduction in coercivity from 60-100 mT for as-prepared samples to 18-33 mT for annealed samples, in a nonlinear manner with respect to RE content. Heating efficiency, i.e., Specific Loss Power (SLP), of all samples has been studied using both magnetometric and calorimetric method to deeper examine the energy loss mechanisms involved.
... Abudayyak et al. [12] revealed the cytotoxicity of CoFe 2 O 4 NPs in diverse cell types and showed that the CoFe 2 O 4 NPs toxicity largely depends on the cell type, concentration, along with administration route. When MagNPs interact with the cell, they can affect the cellular processes by changing the metabolic activity, or through DNA damage [13]. ...
The purpose of this investigation was to examine the effect of Cobalt-Manganese-Zinc Ferrite nanoparticles (Co0.3Mn0.2Zn0.5Fe2O4 NPs) on DNA structure along with its inhibitory role in the growth of T47D cells. This investigation performed with ultraviolet and fluorescence spectroscopy, zeta potential investigation, circular dichroism (CD) spectroscopy, as well as MTT assay, DAPI staining, and flow cytometry analyses. The ultraviolet and fluorescence results indicated that Co0.3Mn0.2Zn0.5Fe2O4 NPs could form a complex via non-intercalative mechanism. The thermodynamics parameters exhibited that Co0.3Mn0.2Zn0.5Fe2O4 NPs the hydrophobic force plays a role in this interaction. The CD data confirmed that Co0.3Mn0.2Zn0.5Fe2O4 NPs induced the transition of DNA conformation to a compact molecular form so-called Ψ-form, furthermore, DNA was relatively thermally stable in the presence of Co0.3Mn0.2Zn0.5Fe2O4 NPs. The anticancer property of Co0.3Mn0.2Zn0.5Fe2O4 NPs via MTT assay, DAPI staining and flow cytometry analyses verified that this nanoparticle can reduce T47D cells proliferation. Based on this investigation Co0.3Mn0.2Zn0.5Fe2O4 NPs could change the structure of DNA and can affect the cell viability. This study can offer an innovative strategy for designing a new anti-tumor agent.
Different types of contaminants are released to wastewater with the rapid
increase in industrial activities, such as heavy metal ions, organics, and hazard organ�isms which are serious harmful to human health. Heavy metal ions, like Pb2+, Cd2+,
Zn2+, and Hg2+ can cause severe health problems in animals and human for its
highly toxic nature. The use of agricultural by-products has been widely investi�gated as an efficient alternative for current costly methods of removing heavy metals
from wastewater. Chemical composition of Rice Straw contains cellulose (32–47%),
hemicellulose (19–27%) and lignin (5–24%). Rice Straw has several characteristics
to predict the functional groups on the surface of the biomass that make it a potential
adsorbent with binding sites capable of taking up metals from aqueous solutions. In
our study, the active sites of Rice Straw were modified using CoFe2O4 nanoparticles
which cause increasing their metal-binding capacity. Adsorption experiments were
carried out using modified Rice Straw to absorb some heavy metals ions like Fe3+,
Mn2+, Cu2+, Cd2+, Zn2+, Ni2+ and Pb2+ from aqueous solution. The prepared samples
were characterized using different analytical techniques. Our results of adsorption
indicated that Rice Straw treated with CoFe2O4 spinel ferrite nanoparticles appeared
to be more efficient to remove heavy metal ions from wastewater
The incidence of female breast cancer has increased; it is the most commonly diagnosed cancer, at 11.7% of the total, and has the fourth highest cancer-related mortality. Magnetic nanoparticles have been used as carriers to improve selectivity and to decrease the side effects on healthy tissues in cancer treatment. Iron oxide (mainly magnetite, Fe3O4), which presents a low toxicity profile and superparamagnetic behavior, has attractive characteristics for this type of application in biological systems. In this article, synthesis and characterization of magnetite (NP-Fe3O4) and silica-coated magnetite (NP-Fe3O4/SiO2) nanoparticles, as well as their biocompatibility via cellular toxicity tests in terms of cell viability, are carefully investigated. MCF-7 cells, which are commonly applied as a model in cancer research, are used in order to define prognosis and treatment specifics at a molecular level. In addition, HaCaT cells (immortalized human keratinocytes) are tested, as they are normal, healthy cells that have been used extensively to study biocompatibility. The results provide insight into the applicability of these magnetic nanoparticles as a drug carrier system. The cytotoxicity of nanoparticles in breast adenocarcinoma (MCF-7) and HaCat cells was evaluated, and both nanoparticles, NP-Fe3O4/SiO2 and NP-Fe3O4, show high cell viability (non-cytotoxicity). After loading the anti-tumor drug doxorubicin (Dox) on NP-Fe3O4/Dox and NP-Fe3O4/SiO2/Dox, the cytotoxicity against MCF-7 cells increases in a dose-dependent and time-dependent manner at concentrations of 5 and 10 μg/mL. HaCat cells also show a decrease in cell viability; however, cytotoxicity was less than that found in the cancer cell line. This study shows the biocompatibility of NP-Fe3O4/SiO2 and NP-Fe3O4, highlighting the importance of silica coating on magnetic nanoparticles and reinforcing the possibility of their use as a drug carrier system against breast adenocarcinoma cells (MCF-7).
Cobalt-based nanoparticles (CBNPs) have recently received great attention in biomedical studies; however, the possible biotoxicity of these nanoparticles (NPs) has remained a foremost concern that should be addressed. As surface functionalization is one of the helpful proposed solutions, we aimed to apply Lipoamino acids (LAAs) as a coating agent to improve biocompatibility. To this purpose, cobalt oxide, cobalt ferrite, and iron oxide nanoparticles (IONs) were synthesized with and without 2-amino-hexadecanoic acid coating to assess the impacts of LAA coating on characteristics and biocompatibility of CBNPs in human cells and compare with IONs, a widely used magnetic NPs in biomedicine. Antibacterial activities of NPs were evaluated against four Gram-negative and Gram-positive bacteria species to assess their biointerface interaction with prokaryotic cells. In addition, the antibacterial activities of synthesized NPs were compared to silver NPs, one of the widely used antimicrobial NPs and standard antibiotics (ampicillin. The structural characteristics properties of NPs were analyzed using TEM, FE-SEM, EDS, FTIR, XRD, and VSM. These NPs exhibited sphere-like to polygon-like morphology with desirable mean size. CBNPs displayed dose-dependent cytotoxicity and antimicrobial activities against human cell lines and all tested microbial species, as well as more cytotoxicity and bacterial inhibition compared to IONs. Besides, the results revealed that LAA coating could significantly improve the biocompatibility and antibacterial activity of NPs while impacting magnetic properties. To sum up, it seems that surface functionalization could provide more potent tools for bioapplications with improving biocompatibility and bacterial inhibition of CBNPs, though; further studies are needed in this regard.
Pyrethrum extract (PE), an important natural bioinsecticide, is extensively used across the world to control pest insects in homes and farms. The aim of this study was to evaluate the potential cytotoxic effect of PE using MTT assay and genotoxic effect using micronucleus (MN) assay. The changes in the expressions of the apoptosis genes in mRNA levels were also investigated using Real-Time qPCR analysis as well as the ratio of apoptotic/necrotic cells with AnnexinV-FITC/Propidium iodide (PI) assay in HepG2 cells. PE markedly suppressed the cell proliferation on HepG2 cells. It significantly increased the frequency of micronucleus (MN) at 500 and 1000 µg/mL. PE also induced the percentage of the cell population of late apoptotic/necrotic cells (FITC + PI+) and necrotic cells (FITC- PI+), especially at 4000 μg/mL analyzed by flow cytometry. PE caused significant fold changes in the expression of several apoptotic genes including APAF1, BIK, BAX, BAD, BİD, MCL-1, CASP3, CASP1, CASP2, FAS, FADD and TNFRSF1A. In particular, the pro-apoptotic gene Hrk (Harakiri) remarkably and dose-dependently was overexpressed of the mRNA level. As a result, PE may exhibit cyto-genotoxic effects, especially at higher concentrations and lead to significant changes in the expression of mRNA levels in several apoptotic genes.
• Highlights
• Natural bioinsecticide PE exhibited a cytotoxic effect in HepG2 cells.
• PE significantly induced the micronucleus (MN) frequency at 500 and 1000 µg/mL.
• This bioinsecticide induced cell death and it lead to significant fold changes in the expression of mRNA levels in several apoptotic genes in HepG2 cells.
• The highest increase of the expression of mRNA levels was determined in Hrk (Harakiri) at 4000 µg/mL.
In recent years, engineered smart nanomaterials are considered ideal candidates for the efficient treatment of cancers. Among all the engineered nanomaterials, gold nanomaterials (AuNPs) have been widely explored to thermal destruction of cancer due to their intrinsic properties such as optical, electronic, photothermal heating ability, physicochemical, and surface plasmon resonance (SPR), which can be altered by changing the size, shape, and aspect ratio of AuNPs. In this book chapter, we mainly focus on four different types of cancer therapies such as AuNP-mediated photothermal therapy, photodynamic therapy, radiotherapy, and glucose-starvation therapy. We begin with an introduction to the properties of the AuNPs and the heat-generating mechanism, which have been well established. Additionally, we also discuss the recent research findings with representative near-infrared-active AuNPs, including spherical nanoparticles, nanoshells, nanorods, nanostars, and nanocages. This includes in vitro and in vivo studies and the recent progression of AuNPs in cancer therapies.
Controlling the moisture level in air and gases is an important aspect in defense, weather station, industry, laboratory and healthcare systems. The accurate measurement and sensing of the humidity/moisture level in the surrounding environment can help to maintain the temperature level for ideal living conditions; from a safety point of view, it can help to prevent the virus/disease transmission; importantly, it can protect expensive equipment, electronic devices and optical devices against damage which are sensitive to high humidity in the atmosphere. The controlled monitoring, regulation and management of humidity necessarily require humidity sensors with high sensitivity, high stability and low response time. Currently, there are various types of humidity sensors available in the market, but there are always limitations on the practical applications as the main problems are associated with their eco-friendly nature, cost, sensitivity, response time (rapid action) and lifetime. Aiming to address these issues, the spinel ferrite nanostructures arise as promising nanomaterials due to their moderate semiconducting features with high resistance, porous nature and high surface activities enabling easy fabrication of the humidity sensors. This chapter provides an overview of the role of spinel ferrite nanostructures for their applications in humidity sensors.
There are many conventional ways of producing energy at large scales such as fossil fuels, hydroelectric power station, wind energy, solar cell plants, marine energy, etc., but most of these require bulky plantation, huge manpower, wide land occupation and are non-portable and expensive to handle too. In the twenty-first century, there is still a huge gap between worldwide energy supply and its demand. The advances in the technology sector have also increased the consumption of energy, but the sources of generating the renewable energy remain limited. In order to account for these problems in recent years, several methods have been adopted and a significant research in this direction has been made by the invention of the hydroelectric cell by Dr. R. K. Kotnala’s group in 2016. Instead of using the magnetic character in the ferrite nanostructures, these nanomaterials were first time effectively exploited for direct energy harvesting application by using their capability to dissociate the absorbed water molecules on its porous surface. This allows the production of ions, which is then followed by the charge transfer of hydronium, hydroxyl and hydrogen ions between the electrodes of the ferrite nanostructures and results in the generation of an electric current across the circuit. The concept of the hydroelectric cell is new, and these cells are easily portable, inexpensive, biodegradable and eco-friendly in nature. This chapter provides an insight on the concept of spinel ferrite nanostructures for the application in the hydroelectric cell.
Almost 40 years since Eric Drexler’s 1991 MIT dissertation, “Molecular Machinery and Manufacturing with Applications to Computation” (Drexler, Nanosystems: molecular machinery, manufacturing, and computation, Wiley, 1992), a lot of exciting has happened in nanotechnology. By far, this nascent field of technology in combination with biotechnology has contributed heavily in medicine and biomaterials R&D sector, but nanomaterials for “green applications” are still quite away from realization. There are several issues underlying this delay, and these can be classified into two broad categories: (i) issues intrinsic to nanomaterials: associated with sustainable tailor-made production, optimization, scale-up, and stability and (ii) environmental issues of nanomaterials associated with their interaction and safe disposal. To have further clarity on first category above, the major intrinsic issues of nanomaterials are grouped into six attributes of studies. These are composition, synthesis, internal and external properties, stability, toxicity, and lifecycle assessment. Although these appear independent attributes but actually they interact with each other and a term “Ensemble Heterogeneity” (he) is defined here to understand their interdependence. Machine learning (ML) can provide deeper insights into both visible and hidden levels of these interdependencies. In the present chapter, firstly, these six attributes are reviewed and an understanding is developed that these attributes must be studied for hidden parameters and patterns using ML for producing optimized design solutions for nanomaterials. Secondly, an overview of different types of ML approaches is given that can contribute to the development of optimized design of nanomaterials. Finally, life cycle assessment (LCA) of nanomaterials is discussed. LCA is a tool to assess the environmental impact and sustainability of any technology to be “green.”
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Nanoparticles with general formula CoFe2-xRExO4 (RE = Yb, Dy, Gd; x = 0.0–0.3) were synthesized by the co-precipitation and heat treated for potential application in magnetic hyperthermia. The influence of RE doping on structural, magnetic and thermal properties has been investigated. The RE cations enter the spinel lattice as detected by X-ray diffraction. Thermal treatment leads to thermodynamically stable and relaxed single-phase spinel structures only for lower RE content, x = 0.01–0.05. The annealed samples present higher mass magnetization values up to 83 Am²/kg. In the case of annealed samples saturation magnetization decreases linearly from 83 Am²/kg (x = 0.01) to about 60 Am²/kg (x = 0.30). Thermal treatment induces a reduction in coercivity from 60 to 100 mT for as-prepared samples to 18–33 mT for annealed samples. Heating efficiency, i.e., Specific Loss Power of all samples has been studied using both magnetometric and calorimetric method to examine the energy loss mechanisms.
Controlling the uptake of nanoparticles into cells so as to balance therapeutic effects with toxicity is an essential unsolved problem in the development of nanomedicine technologies. From this point of view, it is useful to use standard nanoparticles to quantitatively evaluate the physical properties of the nanoparticles in solution and in cells, and to analyze the intracellular dynamic motion and distribution of these nanoparticles at a single-particle level. In this study, standard nanoparticles are developed based on a variant silica-based nanoparticle incorporating fluorescein isothiocyanate (FITC) or/and rhodamine B isothiocyanate (RITC) with a variety of accessible diameters and a matching fluorescent cobalt ferrite core-shell structure (Fe2O4/SiO2). The physical and optical properties of the nanoparticles in vitro are fully evaluated with the complementary methods of dynamic light scattering, electron microscopy, and two fluorescence correlation methods. In addition, cell uptake of dual-colored and core/shell nanoparticles via endocytosis in live HeLa cells is detected by fluorescence correlation spectroscopy and electron microscopy, indicating the suitability of the nanoparticles as standards for further studies of intracellular dynamics with multi-modal methods.
Cobalt ferrite (CoFe2O4) has numerous desirable features such as high anisotropy, good magnetic saturation, large coercivity and high mechanical strength. These remarkable characteristics provide extensive employment for their wide application from industrial to biomedical. The present study aims to evaluate the crystal properties, particle size, and morphology of CoFe2O4 nanoparticles prepared by the thermal treatment method and investigates their biocompatibility. XRD and FTIR analyses demonstrated that CoFe2O4 nanoparticles have an inverse cubic spinel crystalline structure. The average size of spherical CoFe2O4 nanoparticles was confirmed by SEM analysis as 58 nm. The cytotoxic effect of CoFe2O4 nanoparticles was evaluated in L929 cells by using the XTT cell viability assay. After 24 h treatment of CoFe2O4 nanoparticles with a concentration between 10 and 1000 µg/ml, the viability of L929 cells did not significantly decrease. It is concluded that growth CoFe2O4 nanoparticles are beneficial materials for use in various biomedical applications.
Nanoparticle‐based magnetic hyperthermia is a well‐known thermal therapy platform studied to treat solid tumors, but its use for monotherapy is limited due to incomplete tumor eradication at hyperthermia temperature (45 °C). It is often combined with chemotherapy for obtaining a more effective therapeutic outcome. Cubic‐shaped cobalt ferrite nanoparticles (Co–Fe NCs) serve as magnetic hyperthermia agents and as a cytotoxic agent due to the known cobalt ion toxicity, allowing the achievement of both heat and cytotoxic effects from a single platform. In addition to this advantage, Co–Fe NCs have the unique ability to form growing chains under an alternating magnetic field (AMF). This unique chain formation, along with the mild hyperthermia and intrinsic cobalt toxicity, leads to complete tumor regression and improved overall survival in an in vivo murine xenograft model, all under clinically approved AMF conditions. Numerical calculations identify magnetic anisotropy as the main Co–Fe NCs’ feature to generate such chain formations. This novel combination therapy can improve the effects of magnetic hyperthermia, inaugurating investigation of mechanical behaviors of nanoparticles under AMF, as a new avenue for cancer therapy.
Magnetic nanoparticles (MNPs) have attracted much attention in cancer treatment as drug delivers and imaging contrast agents due to their distinctive performances based on the magnetic property and nanoscale structure. In this review, we aim to comprehensively dissect how the applications of MNPs in targeted therapy and magnetic resonance imaging are achieved and their specificities by focusing on the aspects as follows: (1) several important preparation parameters (pH, temperature, ratio of the reactive substances, etc.) that have crucial effects on properties of MNPs, (2) indispensable treatments to improve the biocompatibility, stability, target ability of MNPs and prolong their circulation time for biomedical applications, (3) the mechanism for MNPs to deliver and release medicine to the desired sites and be applied in magnetic hyperthermia as well as related updated research advancements, (4) comparatively promising research directions of MNPs in magnetic resonance imaging, and (5) perspectives in further optimization of their preparations, pre-treatments and applications in cancer diagnosis and therapy.
Efficient and selective removal of azo dyes from water by amine-functionalized-CoFe 2 O 4 nanoparticles reliant on structural features such as size, charge, hydrophobicity/hydrophilicity, and S/C atoms.
Advances in the chemistry and technology of nanomaterials whose sizes are less than 100 nm in at least one dimension led to exponential development in many fields of science and industry [1–19].
We have studied in vitro toxicity of iron oxide nanoparticles (NPs) coated with a thin silica shell (Fe3O4/SiO2 NPs) on A549 and HeLa cells. We compared bare and surface passivated Fe3O4/SiO2 NPs to evaluate the effects of the coating on the particle stability and toxicity. NPs cytotoxicity was investigated by cell viability, membrane integrity, mitochondrial membrane potential (MMP), reactive oxygen species (ROS) assays, and their genotoxicity by comet assay. Our results show that NPs surface passivation reduces the oxidative stress and alteration of iron homeostasis and, consequently, the overall toxicity, despite bare and passivated NPs show similar cell internalization efficiency. We found that the higher toxicity of bare NPs is due to their stronger in-situ degradation, with larger intracellular release of iron ions, as compared to surface passivated NPs. Our results indicate that surface engineering of Fe3O4/SiO2 NPs plays a key role in improving particles stability in biological environments reducing both cytotoxic and genotoxic effects.
The nanotechnology industry is rapidly growing and promises that the substantial changes that will have significant economic and scientific impacts be applicable to a wide range of areas, such as aerospace engineering, nano-electronics, environmental remediation and medical healthcare. In this area, cobalt ferrite nanoparticles have been regarded as one of the competitive candidates because of their suitable physical, chemical and magnetic properties like the high anisotropy constant, high coercivity and high Curie temperature, moderate saturation magnetization and ease of synthesis. This paper introduces the magnetic properties, synthesis methods and some medical applications, including the hyperthermia, magnetic resonance imaging (MRI), magnetic separation and drug delivery of cobalt ferrite nanoparticles.
In recent years, nanoparticles (NPs) and related applications have become an intensive area of research, especially in the biotechnological and biomedical fields, with magnetic NPs being one of the promising tools for tumor treatment and as MRI-contrast enhancers. Several internalization and cytotoxicity studies have been performed, but there are still many unanswered questions concerning NP interactions with cells and NP stability. In this study, we prepared functionalized magnetic NPs coated with polyacrylic acid, which were stable in physiological conditions and which were also nontoxic short-term. Using fluorescence, scanning, and transmission electron microscopy, we were able to observe and determine the internalization pathways of polyacrylic acid–coated NPs in Chinese hamster ovary cells. With scanning electron microscopy we captured what might be the first step of NPs internalization – an endocytic vesicle in the process of formation enclosing NPs bound to the membrane. With fluorescence microscopy we observed that NP aggregates were rapidly internalized, in a time-dependent manner, via macropinocytosis and clathrin-mediated endocytosis. Inside the cytoplasm, aggregated NPs were found enclosed in acidified vesicles accumulated in the perinuclear region 1 hour after exposure, where they stayed for up to 24 hours. High intracellular loading of NPs in the Chinese hamster ovary cells was obtained after 24 hours, with no observable toxic effects. Thus polyacrylic acid–coated NPs have potential for use in biotechnological and biomedical applications.
Many types of nanoparticles (NPs) are tested for use in medical products, particularly in imaging and gene and drug delivery. For these applications, cellular uptake is usually a prerequisite and is governed in addition to size by surface characteristics such as hydrophobicity and charge. Although positive charge appears to improve the efficacy of imaging, gene transfer, and drug delivery, a higher cytotoxicity of such constructs has been reported. This review summarizes findings on the role of surface charge on cytotoxicity in general, action on specific cellular targets, modes of toxic action, cellular uptake, and intracellular localization of NPs. Effects of serum and intercell type differences are addressed. Cationic NPs cause more pronounced disruption of plasma-membrane integrity, stronger mitochondrial and lysosomal damage, and a higher number of autophagosomes than anionic NPs. In general, nonphagocytic cells ingest cationic NPs to a higher extent, but charge density and hydrophobicity are equally important; phagocytic cells preferentially take up anionic NPs. Cells do not use different uptake routes for cationic and anionic NPs, but high uptake rates are usually linked to greater biological effects. The different uptake preferences of phagocytic and nonphagocytic cells for cationic and anionic NPs may influence the efficacy and selectivity of NPs for drug delivery and imaging.
Gold colloids have been homogeneously coated with silica using the silane coupling agent (3-aminopropyl)-trimethoxysilane as a primer to render the gold surface vitreophilic. After the formation of a thin silica layer in aqueous solution, the particles can be transferred into ethanol for further growth using the Stöber method. The thickness of the silica layer can be completely controlled, and (after surface modification) the particles can be transferred into practically any solvent. Varying the silica shell thickness and the refractive index of the solvent allows control over the optical properties of the dispersions. The optical spectra of the coated particles are in good agreement with calculations using Mie's theory for core-shell particles.
An understanding of the interactions between nanoparticles and biological systems is of significant interest. Studies aimed at correlating the properties of nanomaterials such as size, shape, chemical functionality, surface charge, and composition with biomolecular signaling, biological kinetics, transportation, and toxicity in both cell culture and animal experiments are under way. These fundamental studies will provide a foundation for engineering the next generation of nanoscale devices. Here, we provide rationales for these studies, review the current progress in studies of the interactions of nanomaterials with biological systems, and provide a perspective on the long-term implications of these findings.
Nanoparticle toxicology, an emergent field, works toward establishing the hazard of nanoparticles, and therefore their potential risk, in light of the increased use and likelihood of exposure. Analytical chemists can provide an essential tool kit for the advancement of this field by exploiting expertise in sample complexity and preparation as well as method and technology development. Herein, we discuss experimental considerations for performing in vitro nanoparticle toxicity studies, with a focus on nanoparticle characterization, relevant model cell systems, and toxicity assay choices. Additionally, we present three case studies (of silver, titanium dioxide, and carbon nanotube toxicity) to highlight the important toxicological considerations of these commonly used nanoparticles.
Magnetic nanoparticles [MNPs] made from iron oxides have many applications in biomedicine. Full understanding of the interactions between MNPs and mammalian cells is a critical issue for their applications. In this study, MNPs were coated with poly(ethylenimine) [MNP-PEI] and poly(ethylene glycol) [MNP-PEI-PEG] to provide a subtle difference in their surface charge and their cytotoxicity which were analysed by three standard cell viability assays: 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium [MTS], CellTiter-Blue and CellTiter-Glo (Promega, Southampton, UK) in SH-SY5Y and RAW 264.7 cells The data were validated by traditional trypan blue exclusion. In comparison to trypan blue manual counting, the MTS and Titer-Blue assays appeared to have consistently overestimated the viability. The Titer-Glo also experienced a small overestimation. We hypothesise that interactions were occurring between the assay systems and the nanoparticles, resulting in incorrect cell viability evaluation. To further understand the cytotoxic effect of the nanoparticles on these cells, reactive oxygen species production, lipid peroxidation and cell membrane integrity were investigated. After pegylation, the MNP-PEI-PEG possessed a lower positive surface charge and exhibited much improved biocompatibility compared to MNP-PEI, as demonstrated not only by a higher cell viability, but also by a markedly reduced oxidative stress and cell membrane damage. These findings highlight the importance of assay selection and of dissection of different cellular responses in in-vitro characterisation of nanostructures.
Magnetic nanoparticles have attracted attention because of their current and potential usefulness as contrast agents for magnetic resonance imaging (MRI) or colloidal mediators for cancer magnetic hyperthermia. This review examines these in vivo applications through an understanding of the involved problems and the current and future possibilities for resolving them. A special emphasis is made on magnetic nanoparticle requirements from a physical viewpoint (e.g. relaxivity for MRI and specific absorption rate for hyperthermia), the factors affecting their biodistribution (e.g. size, surface hydrophobic/hydrophilic balance, etc.) and the solutions envisaged for enhancing their half-life in the blood compartment and targeting tumour cells.
Due to the rapid development of a diverse array of nanoparticles, used in a wide variety of products, there are now many international activities to assess the potential toxicity of these materials. These particles are developed due to properties such as catalytic reactivity, high surface area, light emission properties, and others. Such properties have the potential to interfere in many well-established toxicity testing protocols. This article outlines some of the most frequently used assays to assess the cytotoxity and biological reactivity of nanoparticles in vitro. The article identifies key issues that need to be addressed in relation to inclusion of relevant controls, assessing particles for their ability to interfere in the assays, and using systematic approaches to prevent misinterpretation of data. The protocols discussed range from simple cytotoxicity assays, to measurement of reactive oxygen species and oxidative stress, activation of proinflammatory signaling, and finally genotoxicity. The aim of this review is to share knowledge relating to nanoparticle toxicity testing in order to provide advice and support for guidelines, regulatory bodies, and for scientists in general.
The effect of temperature on secretory protein transport was studied by cell fractionation of rat pancreatic lobules, pulse-labeled in vitro with [35S]methionine and chased for 60 min at 16, 20, or 37 degrees C. Chase at 37 degrees C allowed secretory proteins to reach a zymogen granule fraction, whereas chase at 16 or 20 degrees C led to their extensive retention in a total microsomal fraction. To pinpoint the sites of transport inhibition, total microsomes were subfractionated by flotation in a sucrose density gradient. Five bands were resolved, of which the heaviest or B1 (density = 1.20 g/ml) consisted primarily of rough microsomes. The lighter fractions, B2 (1.17 g/ml), B3 (1.15 g/ml), and B4 (1.14-1.13 g/ml), consisted primarily of smooth vesicles derived from Golgi elements. B4 had the highest specific activity for galactosyltransferase, a trans Golgi cisternal marker; B2, B3, and B4 are assumed to represent cis, middle, and trans Golgi subcompartments, respectively. At the end of a 2-min pulse, a single peak of labeled proteins colocalized with B1. During subsequent 60-min chases, labeled proteins advanced to B2 at 16 degrees C and to B3 at 20 degrees C. At 37 degrees C the radioactivity remaining in the total microsomal fraction was distributed among four peaks (B1-B4). The results indicate that transport from the endoplasmic reticulum to the Golgi complex is strongly inhibited below 20 degrees C. At 16 degrees C, the bulk of the cohort of labeled secretory proteins is still in the rough endoplasmic reticulum, but its advancing front reaches cis Golgi elements. At 20 degrees C, the front advances to a middle Golgi compartment, and at 37 degrees C most of the cohort (approximately 70%) reaches condensing vacuoles and zymogen granules. It is concluded that transport steps along the endoplasmic reticulum-plasmalemma pathway have distinct temperature requirements.
During the last few years, research on toxicologically relevant properties of engineered nanoparticles has increased tremendously. A number of international research projects and additional activities are ongoing in the EU and the US, nourishing the expectation that more relevant technical and toxicological data will be published. Their widespread use allows for potential exposure to engineered nanoparticles during the whole lifecycle of a variety of products. When looking at possible exposure routes for manufactured Nanoparticles, inhalation, dermal and oral exposure are the most obvious, depending on the type of product in which Nanoparticles are used. This review shows that (1) Nanoparticles can deposit in the respiratory tract after inhalation. For a number of nanoparticles, oxidative stress-related inflammatory reactions have been observed. Tumour-related effects have only been observed in rats, and might be related to overload conditions. There are also a few reports that indicate uptake of nanoparticles in the brain via the olfactory epithelium. Nanoparticle translocation into the systemic circulation may occur after inhalation but conflicting evidence is present on the extent of translocation. These findings urge the need for additional studies to further elucidate these findings and to characterize the physiological impact. (2) There is currently little evidence from skin penetration studies that dermal applications of metal oxide nanoparticles used in sunscreens lead to systemic exposure. However, the question has been raised whether the usual testing with healthy, intact skin will be sufficient. (3) Uptake of nanoparticles in the gastrointestinal tract after oral uptake is a known phenomenon, of which use is intentionally made in the design of food and pharmacological components. Finally, this review indicates that only few specific nanoparticles have been investigated in a limited number of test systems and extrapolation of this data to other materials is not possible. Air pollution studies have generated indirect evidence for the role of combustion derived nanoparticles (CDNP) in driving adverse health effects in susceptible groups. Experimental studies with some bulk nanoparticles (carbon black, titanium dioxide, iron oxides) that have been used for decades suggest various adverse effects. However, engineered nanomaterials with new chemical and physical properties are being produced constantly and the toxicity of these is unknown. Therefore, despite the existing database on nanoparticles, no blanket statements about human toxicity can be given at this time. In addition, limited ecotoxicological data for nanomaterials precludes a systematic assessment of the impact of Nanoparticles on ecosystems.
Biocompatible silica-overcoated magnetic nanoparticles containing an organic fluorescence dye, rhodamine B isothiocyanate (RITC), within a silica shell [50 nm size, MNP@SiO2(RITC)s] were synthesized. For future application of the MNP@SiO2(RITC)s into diverse areas of research such as drug or gene delivery, bioimaging, and biosensors, detailed information of the cellular uptake process of the nanoparticles is essential. Thus, this study was performed to elucidate the precise mechanism by which the lung cancer cells uptake the magnetic nanoparticles. Lung cells were chosen for this study because inhalation is the most likely route of exposure and lung cancer cells were also found to uptake magnetic nanoparticles rapidly in preliminary experiments. The lung cells were pretreated with different metabolic inhibitors. Our results revealed that low temperature disturbed the uptake of magnetic nanoparticles into the cells. Metabolic inhibitors also prevented the delivery of the materials into cells. Use of TEM clearly demonstrated that uptake of the nanoparticles was mediated through endosomes. Taken together, our results demonstrate that magnetic nanoparticles can be internalized into the cells through an energy-dependent endosomal-lysosomal mechanism.
Rapid development of nanoparticles for biomedical applications has, to a large extent, been based on a solid analytical foundation built in the previous decades. Such widespread methods are transmission electron microscopy (TEM), scanning electron microscopy (SEM), and inductively coupled plasma mass spectrometry (ICP-MS). A variety of elemental analysis methods are used to both determine the presence of an element in a sample and quantify how much of said element is present. As material properties at the nanoscale often differ from properties at micro- and macroscales, great attention is often paid to particle sizing analysis. One of the most commonly used surface analysis tools is scanning probe microscopy (SPM). Radioactivity measurement involves detection of “radioactive decay” of the radionuclide. A magnetic resonance imaging (MRI) system consists of a wide variety of components working together to form the desired images.
Gene therapy is defined as the direct transfer of genetic material to tissues or cells for the treatment of inherited disorders and acquired diseases. For gene delivery, magnetic nanoparticles (MNPs) are typically combined with a delivery platform to encapsulate the gene, and promote cell uptake. Delivery technologies that have been used with MNPs contain polymeric, viral, as well as non-viral platforms. In this review, we focus on targeted gene delivery using MNPs.
We report the use of arginine-glycine-aspartic (Arg-Gly-Asp, RGD) peptide-modified dendrimer-entrapped gold nanoparticles (Au DENPs) for highly efficient and specific gene delivery to stem cells. In this study, generation 5 poly(amidoamine) dendrimers modified with RGD via a poly(ethylene glycol) (PEG) spacer and with PEG monomethyl ether were used as templates to entrap gold nanoparticles (AuNPs). The native and the RGD-modified PEGylated dendrimers and the respective well characterized Au DENPs were used as vectors to transfect human mesenchymal stem cells (hMSCs) with plasmid DNA (pDNA) carrying both the enhanced green fluorescent protein and the luciferase (pEGFPLuc) reporter genes, as well as pDNA encoding the human bone morphogenetic protein-2 (hBMP-2) gene. We show that all vectors are capable of transfecting the hMSCs with both pDNAs. Gene transfection using pEGFPLuc was demonstrated by quantitative Luc activity assay and qualitative evaluation by fluorescence microscopy. For the transfection with hBMP-2, the gene delivery efficiency was evaluated by monitoring the hBMP-2 concentration and the level of osteogenic differentiation of the hMSCs via alkaline phosphatase activity, osteocalcin secretion, calcium deposition, and von Kossa staining assays. Our results reveal that the stem cell gene delivery efficiency is largely dependent on the composition and the surface functionality of the dendrimer-based vectors. The coexistence of RGD and AuNPs rendered the designed dendrimeric vector with specific stem cell binding ability likely via binding of integrin receptor on the cell surface and improved 3-dimensional conformation of dendrimers, which is beneficial for highly efficient and specific stem cell gene delivery applications.
We report the evolution of the protein secondary structure of HSA adsorbed on AuNPs over time. This evolution is in agreement with the S-Au interaction time determined by Raman spectroscopy. The results indicate that the changes in the secondary structure of HSA are induced by the S-Au interaction.
Background:
Single cell gel electrophoresis, or the comet assay, was devised as a sensitive method for detecting DNA strand breaks, at the level of individual cells. A simple modification, incorporating a digestion of DNA with a lesion-specific endonuclease, makes it possible to measure oxidised bases.
Scope of review:
With the inclusion of formamidopyrimidine DNA glycosylase to recognise oxidised purines, or Nth (endonuclease III) to detect oxidised pyrimidines, the comet assay has been used extensively in human biomonitoring to monitor oxidative stress, usually in peripheral blood mononuclear cells.
Major conclusions:
There is evidence to suggest that the enzymic approach is more accurate than chromatographic methods, when applied to low background levels of base oxidation. However, there are potential problems of over-estimation (because the enzymes are not completely specific) or under-estimation (failure to detect lesions that are close together). Attempts have been made to improve the inter-laboratory reproducibility of the comet assay.
General significance:
In addition to measuring DNA damage, the assay can be used to monitor the cellular or in vitro repair of strand breaks or oxidised bases. It also has applications in assessing the antioxidant status of cells. In its various forms, the comet assay is now an invaluable tool in human biomonitoring and genotoxicity testing. This article is part of a Special Issue entitled Current methods to study reactive oxygen species - pros and cons and biophysics of membrane proteins. Guest Editor: Christine Winterbourn.
Precise control over the synthesis conditions and surface functionalization of MNPs is crucial because it governs their physicochemical properties, their colloidal stability, and their biological behavior/fate. For pharmaceutical and biomedical purposes, magnetic platforms should possess very small size and narrow size distribution together with high magnetization values. Alternatively, great interest has been recently devoted to the development of metal-doped iron oxides with enhanced magnetic properties. The control over the characteristics and structure of the gel can be easily obtained by fixing the hydroxylation and condensation conditions, as well as the kinetics of the growing process. In particular, the pH, the temperature, the nature and concentration of the salt precursors, and the nature of the solvent have been described to influence the synthesis process. Practically, NP formation occurs when the metal precursor is suspended in polyol and heated up to its boiling point, under stirring.
Although a growing number of innovations have emerged in the fields of nanobiotechnology and nanomedicine, new engineered nanomaterials (ENMs) with novel physicochemical properties are posing novel challenges to understand the full spectrum of interactions at the nano–bio interface. Because these could include potentially hazardous interactions, researchers need a comprehensive understanding of toxicological properties of nanomaterials and their safer design. In depth research is needed to understand how nanomaterial properties influence bioavailability, transport, fate, cellular uptake, and catalysis of injurious biological responses. Toxicity of ENMs differ with their size and surface properties, and those connections hold true across a spectrum of in vitro to in vivo nano–bio interfaces. In addition, the in vitro results provide a basis for modeling the biokinetics and in vivo behavior of ENMs. Nonetheless, we must use caution in interpreting in vitro toxicity results too literally because of dosimetry differences between in vitro and in vivo systems as well the increased complexity of an in vivo environment.
Monodisperse mesoporous silica (mSiO(2) ) coated superparamagnetic iron oxide (Fe(3) O(4) @mSiO(2) ) nanoparticles (NPs) have been developed as a potential magnetic resonance imaging (MRI) T(2) contrast agent. To evaluate the effect of surface coating on MRI contrast efficiency, we examined the proton relaxivities of Fe(3) O(4) @mSiO(2) NPs with different coating thicknesses. It was found that the mSiO(2) coating has a significant impact on the efficiency of Fe(3) O(4) NPs for MRI contrast enhancement. The efficiency increases with the thickness of mSiO(2) coating and is much higher than that of the commercial contrast agents. Nuclear magnetic resonance (NMR) relaxometry of Fe(3) O(4) @mSiO(2) further revealed that mSiO(2) coating is partially permeable to water molecules and therefore induces the decrease of longitudinal relaxivity, r(1) . Biocompatibility evaluation of various sized (ca. 35-95 nm) Fe(3) O(4) @mSiO(2) NPs was tested on OC-k3 cells and the result showed that these particles have no negative impact on cell viability. The enhanced MRI efficiency of Fe(3) O(4) @mSiO(2) highlights these core-shell particles as highly efficient T(2) contrast agents with high biocompatibility.
The antitumor effect of a magnetic fluid was studied after direct inoculation into cat mammary tumors. An external magnetic field was used to retain the nanoparticles in the tumor tissue. After 2 month, the mammary tumor regressed very much in size and the microscopic exam revealed that the tumor cells massively endocytosed magnetic nanoparticles and entered in lysis process.
Nanomaterials offer opportunities to construct novel compounds for many different fields. Applications include devices for energy, including solar cells, batteries, and fuel cells, and for health, including contrast agents and mediators for photodynamic therapy and hyperthermia. Despite these promising applications, any new class of materials also bears a potential risk for human health and the environment. The advantages and innovations of these materials must be thoroughly compared against risks to evaluate each new nanomaterial. Although nanomaterials are often used intentionally, they can also be released unintentionally either inside the human body, through wearing of a prosthesis or the inhalation of fumes, or into the environment, through mechanical wear or chemical powder waste. This possibility adds to the importance of understanding potential risks from these materials.
Nanomaterials have been widely evaluated for potential use as efficient delivery carriers for cancer diagnosis and therapy. To translate these nanomaterials to the clinic, their safety needs to be verified, particularly in terms of genotoxicity and cytotoxicity. We investigated changes in gene expression profiles influenced by silica-coated cobalt ferrite magnetic-fluorescence nanoparticles and silica-free cobalt ferrite magnetic-core nanoparticles in vivo and in vitro.
(68)Ga-labeled cobalt ferrite nanoparticles produced by synthesis of 2-(p-isothio-cyanatobenzyl)-1,4,7-triazacyclonane-1,4,7-triacetic acid chelator were established after labeling efficiency had been validated through a thin-layer chromatography method. The expression of genes associated with the stress and toxicity pathways was verified by a commercially available polymerase chain reaction array kit.
In comparison with magnetic-fluorescence nanoparticles, magnetic-core nanoparticles revealed severe cytotoxic effects at various doses and treatment times as determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Whole-body small-animal PET and biodistribution studies, including transmission electron microscope analysis, showed that tail-vein injection of magnetic-core or magnetic-fluorescence nanoparticles exhibited substantial liver accumulation. Real-time polymerase chain reaction array using 52 genes related to cellular toxicity demonstrated that 17 genes from the magnetic-core-treated liver samples were significantly affected, mostly in relation to DNA damage or repair and to oxidative or metabolic stress. The magnetic-fluorescence-treated liver samples showed gene expression approximately 90% similar to that of untreated liver samples.
We compared a variety of gene expression profiles in mice injected with magnetic-fluorescence or magnetic-core nanoparticles. This study of gene expression profiles affected by nanotoxicity provides critical information for the clinical use of silica-coated cobalt ferrite.
Small interfering RNA (siRNA) technology holds great promise as a therapeutic intervention for targeted gene silencing in cancer and other diseases. However, in vivo systemic delivery of siRNA-based therapeutics to tumour tissues/cells remains a challenge. The major limitations against the use of siRNA as a therapeutic tool are its degradation by serum nucleases, poor cellular uptake and rapid renal clearance following systemic administration. Several siRNA-based loco-regional therapeutics are already in clinical trials. Further development of siRNAs for anti-cancer therapy depends on the development of safe and effective nanocarriers for systemic administration. To overcome these hurdles, nuclease-resistant chemically modified siRNAs and variety of synthetic and natural biodegradable lipids and polymers have been developed to systemically deliver siRNA with different efficacy and safety profiles. Cationic liposomes have emerged as one of the most attractive carriers because of their ability to form complexes with negatively charged siRNA and high in vitro transfection efficiency. However, their effectiveness as potential therapeutic carriers is limited by potential for pulmonary toxicity. Recently, our laboratories described the use of neutral 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine based nanoliposomes in murine tumour models. We found this approach to be safe and 10- and 30-fold more effective than cationic liposomes and naked siRNA, respectively, for systemic delivery of siRNA into tumour tissues. Here, we review potential approaches for systemic delivery of siRNA for cancer therapy.
The development of nanoparticles for biomedical applications including medical imaging and drug delivery is currently undergoing a dramatic expansion. However, as the range of nanoparticle types and applications increases, it is also clear that the potential toxicities of these novel materials and the properties driving such toxic responses must also be understood. Indeed, a detailed assessment of the factors that influence the biocompatibility and/or toxicity of nanoparticles is crucial for the safe and sustainable development of the emerging nanotechnologies. This review summarizes some of the recent developments in the field of nanomedicine with particular emphasis on inorganic nanoparticles for drug delivery. The synthesis routes, physico-chemical characteristics, and cytotoxic properties of inorganic nanoparticles are thus explored and lessons learned from the toxicological investigation of three common types of engineered nanomaterials of titania, gold, and mesoporous silica are discussed. Emphasis is placed on the recognition versus non-recognition of engineered nanomaterials by the immune system, the primary surveillance system against microorganisms and particles, which, in turn, is intimately linked to the issue of targeted drug delivery using such nanomaterials as carrier systems.
In this study, we present in vitro cytotoxicity of iron oxide (Fe(3)O(4)) and manganese oxide (MnO) using live/dead cell assay, lactate dehydrogenase assay, and reactive oxygen species detection with variation of the concentration of nanoparticles (5-500 microg/ml), incubation time (18-96 h), and different human cell lines (lung adenocarcinoma, breast cancer cells, and glioblastoma cells). The surface of nanoparticles is modified with polyethyleneglycol-derivatized phospholipid to enhance the biocompatibility, water-solubility, and stability under an aqueous media. While the cytotoxic effect was negligible for 18 h incubation even at highest concentration of 500 microg/ml, MnO nanoparticle represented higher level of toxicity than those of Fe(3)O(4) and the commercial medical contrast reagent, Feridex after 2 and 4 day incubation time. However, the cytotoxicity of Fe(3)O(4) is equivalent or better than Feridex based on the live/dead cell viability assay. The engineered MnO and Fe(3)O(4) exhibited excellent stability compared with Feridex for a prolonged incubation time.
With the rapid expansion in the nanotechnology industry, it is essential that the safety of engineered nanomaterials and the factors that influence their associated hazards are understood. A vital area governing regulatory health risk assessment is genotoxicology (the study of genetic aberrations following exposure to test agents), as DNA damage may initiate and promote carcinogenesis, or impact fertility. Of late, considerable attention has been given to the toxicity of engineered nanomaterials, but the importance of their genotoxic potential on human health has been largely overlooked. This comprehensive review focuses on the reported abilities of metal nanoparticles, metal-oxide nanoparticles, quantum dots, fullerenes, and fibrous nanomaterials, to damage or interact with DNA, and their ecogenotoxicity is also considered. Many of the engineered nanomaterials assessed were found to cause genotoxic responses, such as chromosomal fragmentation, DNA strand breakages, point mutations, oxidative DNA adducts and alterations in gene expression profiles. However, there are clear inconsistencies in the literature and it is difficult to draw conclusions on the physico-chemical features of nanomaterials that promote genotoxicity, largely due to study design. Hence, areas that require that further attention are highlighted and recommendations to improve our understanding of the genotoxic potential of engineered nanomaterials are addressed.
In this study, multifunctional nanoparticles containing thermosensitive polymers grafted onto the surfaces of 6-nm monodisperse Fe(3)O(4) magnetic nanoparticles coated by silica were synthesized using reverse microemulsions and free radical polymerization. The magnetic properties of SiO(2)/Fe(3)O(4) nanoparticles show superparamagnetic behavior. Thermosensitive PNIPAM (poly(N-isopropylacrylamide)) was then grafted onto the surfaces of SiO(2)/Fe(3)O(4) nanoparticles, generating thermosensitive and magnetic properties of nanocomposites. The sizes of fabricated nanoparticles with core-shell structure are controlled at about 30 nm and each nanoparticle contains only one monodisperse Fe(3)O(4) core. For thermosensitivity analysis, the phase transition temperatures of multifunctional nanoparticles measured using DSC was at around 34-36 degrees C. The magnetic characteristics of these multifunctional nanoparticles were also superparamagnetic.
A new tetrazolium salt XTT, sodium 3'-[1-[(phenylamino)-carbonyl]-3,4-tetrazolium]-bis(4-methoxy-6- nitro)benzene-sulfonic acid hydrate, was evaluated for use in a colorimetric assay for cell viability and proliferation by normal activated T cells and several cytokine dependent cell lines. Cleavage of XTT by dehydrogenase enzymes of metabolically active cells yields a highly colored formazan product which is water soluble. This feature obviates the need for formazan crystal solubilization prior to absorbance measurements, as required when using other tetrazolium salts such as MTT. Bioreduction of XTT by all the murine cells examined was not particularly efficient, but could be potentiated by addition of electron coupling agents such as phenazine methosulfate (PMS) or menadione (MEN). Optimal concentrations of PMS or MEN were determined for the metabolism of XTT by the T cell lines HT-2 and 11.6, NFS-60 a myeloid leukemia, MC/9 a mast cell line and mitogen activated splenic T cells. When used in combination with PMS, each of these cells generated higher formazan absorbance values with XTT than were observed with MTT. Thus the use of XTT in colorimetric proliferation assays offer significant advantages over MTT, resulting from reduced assay time and sample handling, while offering equivalent sensitivity.
The alkaline microgel electrophoresis technique was modified to achieve a substantial increase in sensitivity for the detection of radiation-induced DNA damage in human lymphocytes. This increased sensitivity was achieved through: (1) the addition of free radical scavengers to the electrophoresis solution to reduce DNA damage generated during alkaline unwinding and electrophoresis; (2) the modification of the electrophoresis unit to achieve a more uniform electric field; (3) the use of YOYO-1, a DNA dye, producing fluorescence 500-fold more intense than ethidium bromide; and (4) the introduction of an image analysis system for the quantitation of DNA migration. In addition to increasing sensitivity, these modifications have increased the speed with which observations can be quantified, and improved reproducibility from experiment to experiment. In human lymphocytes, these modifications have resulted in an increased sensitivity of several fold, allowing the detection of DNA damage in the range of 50 mGy. This increased sensitivity for the detection of DNA damage should extend the utility of this technique.
The study of DNA damage at the chromosome level is an essential part of genetic toxicology because chromosomal mutation is an important event in carcinogenesis. The micronucleus assays have emerged as one of the preferred methods for assessing chromosome damage because they enable both chromosome loss and chromosome breakage to be measured reliably. Because micronuclei can only be expressed in cells that complete nuclear division a special method was developed that identifies such cells by their binucleate appearance when blocked from performing cytokinesis by cytochalasin-B (Cyt-B), a microfilament-assembly inhibitor. The cytokinesis-block micronucleus (CBMN) assay allows better precision because the data obtained are not confounded by altered cell division kinetics caused by cytotoxicity of agents tested or sub-optimal cell culture conditions. The method is now applied to various cell types for population monitoring of genetic damage, screening of chemicals for genotoxic potential and for specific purposes such as the prediction of the radiosensitivity of tumours and the inter-individual variation in radiosensitivity. In its current basic form the CBMN assay can provide, using simple morphological criteria, the following measures of genotoxicity and cytotoxicity: chromosome breakage, chromosome loss, chromosome rearrangement (nucleoplasmic bridges), cell division inhibition, necrosis and apoptosis. The cytosine-arabinoside modification of the CBMN assay allows for measurement of excision repairable lesions. The use of molecular probes enables chromosome loss to be distinguished from chromosome breakage and importantly non-disjunction in non-micronucleated binucleated cells can be efficiently measured. The in vitro CBMN technique, therefore, provides multiple and complementary measures of genotoxicity and cytotoxicity which can be achieved with relative ease within one system. The basic principles and methods (including detailed scoring criteria for all the genotoxicity and cytotoxicity end-points) of the CBMN assay are described and areas for future development identified.
Reactive oxygen species (ROS) are constantly generated and eliminated in the biological system, and play important roles in a variety of normal biochemical functions and abnormal pathological processes. Growing evidence suggests that cancer cells exhibit increased intrinsic ROS stress, due in part to oncogenic stimulation, increased metabolic activity, and mitochondrial malfunction. Since the mitochondrial respiratory chain (electron transport complexes) is a major source of ROS generation in the cells, the vulnerability of the mitochondrial DNA to ROS-mediated damage appears to be a mechanism to amplify ROS stress in cancer cells. The escalated ROS generation in cancer cells serves as an endogenous source of DNA-damaging agents that promote genetic instability and development of drug resistance. Malfunction of mitochondria also alters cellular apoptotic response to anticancer agents. Despite the negative impacts of increased ROS in cancer cells, it is possible to exploit this biochemical feature and develop novel therapeutic strategies to preferentially kill cancer cells through ROS-mediated mechanisms. This article reviews ROS stress in cancer cells, its underlying mechanisms and relationship with mitochondrial malfunction and alteration in drug sensitivity, and suggests new therapeutic strategies that take advantage of increased ROS in cancer cells to enhance therapeutic activity and selectivity.
The interaction of bovine serum albumin (BSA) with gold colloids and surfaces was studied using zeta-potential and quartz crystal microbalance (QCM) measurements, respectively, to determine the surface charge and coverage. The combination of these two measurements suggests that BSA binding to gold nanoparticles and gold surfaces occurs by an electrostatic mechanism when citrate is present. The binding of BSA to bare gold is nearly two times greater than the binding of BSA to a citrate-coated gold surface, suggesting that protein spreading (denaturation) on the surface may occur followed by secondary protein binding. On the other hand, binding to citrate-coated gold surfaces can be fit to a Langmuir isotherm model to obtain a maximum surface coverage of (3.7 +/- 0.2) x 10(12) molecules/cm(2) and a binding constant of 1.0 +/- 0.3 microM(-1). The zeta-potential measurements show that the stabilization of colloids by BSA has a significant contribution from a steric mechanism because the colloids are stable, even at their isoelectric point (pI approximately 4.6). To be consistent with the observed phenomena, the electrostatic interactions between BSA and citrate must consist of salt-bridges, for example, of the carboxylate-ammonium type, between the citrate and the lysine on the protein surface. The data support the role of strong electrostatic binding but do not exclude contributions from steric or hydrophobic interactions with the surface adlayer.
A novel and simple method to form water-dispersed magnetic nanoparticles was successfully developed through glucosaminic acid-surface modification of iron oxide nanoparticles. The resultant glucosaminic acid-modified magnetic nanoparticles (GA-MNPs) had not only good uniformity in spherical shape with diameter of about 10-13 nm, but also possessed excellent water-dispersity and stability. In cell culture experiments, the internalization of GA-MNPs into different kinds of cells was observed over a 5-day period. The results indicated that the internalization of GA-MNPs into mouse macrophage cells and mouse embryonic fibroblast cells was not observed after 40 h of culturing. However, the GA-MNPs were internalized quickly into cancer cells after just 24 h of culturing. TEM images of the GA-MNPs uptake in ECA-109 cells were used to study the internalization mechanisms of GA-MNPs and their distribution in ECA-109 cells. Additionally, a water-dispersed magnetic capture probe was prepared by immobilization of oligonucleotides onto GA-MNPs, and the probe was used for detection and separation of their complementary oligonucleotides sequence.
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