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Synthesis of Tf-PEG-AuNPs. Unmodified 50-nm AuNPs (I) were reacted with excess mPEG-SH to form PEG-AuNPs (II) as untargeted particles or first were reacted with various amounts of Tf-PEG-SH and later excess mPEG-SH to form Tf-PEG-AuNPs (III: 2 Tf per particle; IV: 18 Tf per particle; V: 144 Tf per particle).
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PEGylated gold nanoparticles are decorated with various amounts of human transferrin (Tf) to give a series of Tf-targeted particles with near-constant size and electrokinetic potential. The effects of Tf content on nanoparticle tumor targeting were investigated in mice bearing s.c. Neuro2A tumors. Quantitative biodistributions of the nanoparticles...
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... For such agents, uptake by TAM is not helpful, because liberated siRNA will not be able to enter cancer cells on its own (unlike, for example, DXR), and also because oncogene knockdown in TAM will not have a therapeutic effect. Ligand-mediated active targeting may help in such situations, beneficially shifting the balance from predominant delivery to TAM towards more efficient delivery to and into cancer cells 37,38 . Our tumour microenvironment biomarkers determining tumour-directed drug delivery complement tissue biomarkers already available in the clinic for patient stratification in case of actively targeted therapeutics (for example, HER2 staining in case of intended treatment with the HER2-targeted antibody-drug conjugates adotrastuzumab emtansine (Kadcyla) or trastuzumab deruxtecan (Enhertu)). ...
The clinical prospects of cancer nanomedicines depend on effective patient stratification. Here we report the identification of predictive biomarkers of the accumulation of nanomedicines in tumour tissue. By using supervised machine learning on data of the accumulation of nanomedicines in tumour models in mice, we identified the densities of blood vessels and of tumour-associated macrophages as key predictive features. On the basis of these two features, we derived a biomarker score correlating with the concentration of liposomal doxorubicin in tumours and validated it in three syngeneic tumour models in immunocompetent mice and in four cell-line-derived and six patient-derived tumour xenografts in mice. The score effectively discriminated tumours according to the accumulation of nanomedicines (high versus low), with an area under the receiver operating characteristic curve of 0.91. Histopathological assessment of 30 tumour specimens from patients and of 28 corresponding primary tumour biopsies confirmed the score’s effectiveness in predicting the tumour accumulation of liposomal doxorubicin. Biomarkers of the tumour accumulation of nanomedicines may aid the stratification of patients in clinical trials of cancer nanomedicines.
... However, Davis et al. had a different but compatible conclusion that TFtargeted NPs could not accumulate more in tumors than nontargeted NPs but provided greater intracellular delivery of therapeutic agents to cancer cells than their nontargeted analogs. [62] ...
Nanodelivery systems (NDSs) provide promising prospects for decreasing drug doses, reducing side effects, and improving therapeutic effects. However, the bioapplications of NDSs are still compromised by their fast clearance, indiscriminate biodistribution, and limited tumor accumulation. Hence, engineering modification of NDSs aiming at promoting tumor‐specific therapy and avoiding systemic toxicity is usually needed. An NDS integrating various functionalities, including flexible camouflage, specific biorecognition, and sensitive stimuli‐responsiveness, into one sequence would be “smart” and highly effective. Herein, we systematically summarize the related principles, methods, and progress. At the end of the review, we predict the obstacles to precise nanoengineering and prospects for the future application of NDSs.
... Blood pharmacokinetics studies how drugs or nanoparticles are processed within the bloodstream. It encompasses the absorption, distribution, metabolism, and elimination (ADME) of these substances in the blood [3]. Understanding the pharmacokinetics of nanoparticles in blood is critically essential for the advancement of nanomedicine. ...
... [35] The admirable properties of gold nanoparticles (AuNPs) have led to widespread belief in their high biocompatibility with mammalian systems, both in vitro and in vivo. [36] Due to their exclusive physicochemical attributes and minimal cytotoxicity, the application of gold nanoparticles (AuNPs) [37,[38][39][40][41][42][43][44] has been extensively implemented in biological and biotechnological fields as biocidal agents, [45] photosensitizers, [46] drug delivery systems [47,48] and molecular diagnostic tools. [49,50] AuNPs as antibacterials face aggregation challenges, addressed by coatings. ...
Strategically controlling concentrations of lipid‐conjugated L‐tryptophan (vsPA) guides the self‐assembly of nanostructures, transitioning from nanorods to fibres and culminating in spherical shapes. The resulting Peptide‐Au hybrids, exhibiting size‐controlled 1D, 2D, and 3D nanostructures, show potential in antibacterial applications. Their high biocompatibility, favourable surface area‐to‐volume ratio, and plasmonic properties contribute to their effectiveness against clinically relevant bacteria. This controlled approach not only yields diverse nanostructures but also holds promise for applications in antibacterial therapeutics.
... NPs and nanocomposites can help open the right junctions to reach the neural cells. Nanoconjugates can also follow the transcytosis process to cross the endothelial cells [54]. Moreover, NPs can be used with receptor-mediated transcytosis to effectively distribute to the brain tissues to treat NDDs. ...
The application of nanoparticles (NPs) in medicine is an emerging field to advance the therapy of diseases that are difficult to treat. NPs are favored as therapeutic drugs because of their nanoscale size, high surface area, amenability to surface modifications, and better effectiveness. Moreover, they can deeply penetrate tissues like the central nervous system (CNS), which are not easily accessible to other drugs. Neurodegenerative diseases (NDDs) are prevalent in many parts of the world. They are characterized by neuronal death and subsequent blockage in optimum neuronal activities. Most prevalent NDDs are Alzheimer’s disease (AD) and Parkinson’s disease (PD). AD is characterized by the abnormal deposition of amyloid proteins, forming plaques around brain cells. PD is caused by the deposition of Lewy bodies. All these toxic buildups of proteins lead to neuronal death. Several metal NPs, nanocomposites, and quantum dots have been tested using human cell lines and animal models to explore their efficacy against the causative factors of NDDs. These NPs showed a positive response in the majority of such experiments. However, most of these experiments are in infancy. Certain concerns regarding toxicity, half-life, and biocompatibility of drugs also persist that need to be addressed in the near future.
... Hepatocellular carcinoma (HCC) is not only the most common form of primary liver cancer, but also the leading cause of cancer-related deaths worldwide. Its pathogenesis is can improve the specificity of the drug cargo towards cancer cells [26,27]. Many studies have used PEGylated liposomes combined with TF and PEG to achieve targetability and longevity for drug delivery to solid tumors [28,29]. ...
Triptolide (TP) is an epoxy diterpene lactone compound isolated and purified from the traditional Chinese medicinal plant Tripterygium wilfordii Hook. f., which has been shown to inhibit the proliferation of hepatocellular carcinoma. However, due to problems with solubility, bioavailability, and adverse effects, the use and effectiveness of the drug are limited. In this study, a transferrin-modified TP liposome (TF-TP@LIP) was constructed for the delivery of TP. The thin-film hydration method was used to prepare TF-TP@LIP. The physicochemical properties, drug loading, particle size, polydispersity coefficient, and zeta potential of the liposomes were examined. The inhibitory effects of TF-TP@LIP on tumor cells in vitro were assessed using the HepG2 cell line. The biodistribution of TF-TP@LIP and its anti-tumor effects were investigated in tumor-bearing nude mice. The results showed that TF-TP@LIP was spherical, had a particle size of 130.33 ± 1.89 nm and zeta potential of −23.20 ± 0.90 mV, and was electronegative. Encapsulation and drug loading were 85.33 ± 0.41% and 9.96 ± 0.21%, respectively. The preparation was stable in serum over 24 h and showed biocompatibility and slow release of the drug. Flow cytometry and fluorescence microscopy showed that uptake of TF-TP@LIP was significantly higher than that of TP@LIP (p < 0.05), while MTT assays indicated mean median inhibition concentrations (IC50) of TP, TP@LIP, and TF-TP@ of 90.6 nM, 56.1 nM, and 42.3 nM, respectively, in HepG2 cell treated for 48 h. Real-time fluorescence imaging indicated a significant accumulation of DiR-labeled TF-TP@LIPs at tumor sites in nude mice, in contrast to DiR-only or DiR-labeled, indicating that modification with transferrin enhanced drug targeting to the tumor tissues. Compared with the TP and TP@LIP groups, the TF-TP@LIP group had a significant inhibitory effect on tumor growth. H&E staining results showed that TF-TP@LIP inhibited tumor growth and did not induce any significant pathological changes in the heart, liver, spleen, and kidneys of nude mice, with all liver and kidney indices within the normal range, with no significant differences compared with the control group, indicating the safety of the preparation. The findings indicated that modification by transferrin significantly enhanced the tumor-targeting ability of the liposomes and improved their anti-tumor effects in vivo. Reducing its distribution in normal tissues and decreasing its toxic effects suggest that the potential of TF-TP@LIP warrants further investigation for its clinical application.
... The conjugation of receptor-specific ligands that can support site-specific targeting is necessary for active targeting. Active targeting can be accomplished by ligand-receptor, antigen-antibody, or aptamer targeting, which all involve molecular recognition of the diseased cells by different signature molecules overexpressed in the diseased region (Choi et al., 2010;Thorpe, 2004). ...
Breast cancer is a commonly known cancer type and the leading cause of cancer death among females. One of the unresolved problems in cancer treatment is the increased resistance of the tumor to existing treatments, which is a direct result of apoptotic defects. Calculating an alternative to cell death (autophagy) may be the ultimate solution to maximizing cancer cell death. Our aim in this study was to investigate the potential of free nanoparticles (un-drug-loaded) in the induction or inhibition of autophagy and consider this effect on the therapy process. When the studies met the inclusion criteria, the full texts of all relevant articles were carefully examined and classified. Of the 25 articles included in the analysis, carried out on MCF-7, MDA-MB-231, MDA-MB-231-TXSA, MDA-MB-468, SUM1315, and 4T1 cell lines. Twenty in vitro studies and five in vivo/in vitro studies applied five different autophagy tests: Acridine orange, western blot, Cyto-ID Autophagy Detection Kit, confocal microscope, and quantitative polymerase chain reaction. Nanoparticles (NPs) in the basic format, including Ag, Au, Y2 O3 , Se, ZnO, CuO, Al, Fe, vanadium pentoxide, and liposomes, were prepared in the included articles. Three behaviors of NPs related to autophagy were seen: induction, inhibition, and no action. Screened and presented data suggest that most of the involved free NPs (metallic NPs) in this systematic review had reactive oxygen species-mediated pathways with autophagy induction (36%). Also, PI3K/Akt/mTOR and MAPK/ERK signaling pathways were mentioned in just four studies (16%). An impressive percentage of studies (31%) did not examine the NP-related autophagy pathway.
... Nanoparticles with a surface more than 200 nm will be absorbed by the Monocular Phagocyte System (MPS) and flow directly towards the Reticuloendothelial system (RES) [18,19]. There has been numerous research and achievements on the effects of size and surface properties of nanoparticles inside an organism [20][21][22], but seldom is there any research on the affect and distribution of different shapes of nanoparticles inside an organism during extraction and drug targeting. Due to the permeation and enhanced permeability and retention effect of tumour cell, nanoparticles will be concentrated near the tumor cells. ...
There has been few research on the affect and distribution of different shapes of nanoparticles inside an organism during extraction and drug targeting. In order to obtain the distribution of magnetic nanoparticles with different morphology and size in vivo, a general method of Re-188 labeled Magnetic Core–Shell Nanoparticles (MNPs) Materials was developed. Based on the prepared magnetic particles with three different morphologies and sizes, including 230 nm spherical Fe3O4@SiO2 particles (S-230), 100 nm spherical Fe3O4@SiO2 particles (S-100) and peanut shaped Fe3O4@SiO2 particles (P-180, the length of the short axis is about 100 nm and the length of the long axis is about 180 nm), the aminated MNPs were labeled with radionuclide Re-188 through the coupling of diethylenetriamine pentaacetic anhydride. The nuclide Re-188 was labeled to investigate their distribution behavior in mice. Most of the small-size particles S-100 can be separated from the capture of the endothelial reticular system and removed by renal metabolism. Most of the larger particles, S-230 and P-180, will be captured by the endothelial reticular system, and the nanoparticles P-180 with large aspect ratio are easier to be captured by the tissue in the spleen and enter the cells through endocytosis.
... When compared to spherical gold particles, the AuNRs have drawn worldwide attention because of their inimitable shape-dependent optical properties. What makes the AuNRs as exclusive materials for biological imaging, sensing, photo thermal therapy, and drug delivery is their ability to possess different plasmon bands [14][15][16][17]. Even though, they have attracting features, their usage is restricted because even a small change in the shape, size, and surface nature will alter their properties which in turn affect their biological applications. ...
... The strategy of using Tf-decorated nanoparticles to target TfRoverexpressing tumor cells has attracted increasing attention in cancer therapy. [244][245][246] Two Tf-guided nanoformulations, denoted as MBP-426 and CALAA-01, have shown great therapeutic potential and entered clinical trials. 247 MBP-426 is an oxaliplatin-loaded liposome that is coupled to transferrin for tumor targeting. ...
Cancer remains a highly lethal disease in the world. Currently, either conventional cancer therapies or modern immunotherapies are non-tumor-targeted therapeutic approaches that cannot accurately distinguish malignant cells from healthy ones, giving rise to multiple undesired side effects. Recent advances in nanotechnology, accompanied by our growing understanding of cancer biology and nano-bio interactions, have led to the development of a series of nanocarriers, which aim to improve the therapeutic efficacy while reducing off-target toxicity of the encapsulated anticancer agents through tumor tissue-, cell-, or organelle-specific targeting. However, the vast majority of nanocarriers do not possess hierarchical targeting capability, and their therapeutic indices are often compromised by either poor tumor accumulation, inefficient cellular internalization, or inaccurate subcellular localization. This Review outlines current and prospective strategies in the design of tumor tissue-, cell-, and organelle-targeted cancer nanomedicines, and highlights the latest progress in hierarchical targeting technologies that can dynamically integrate these three different stages of static tumor targeting to maximize therapeutic outcomes. Finally, we briefly discuss the current challenges and future opportunities for the clinical translation of cancer nanomedicines.
