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Histological observations of spleen, liver, kidney and heart of the Ctrl and CNT group on day 2, 7, 30, 60 and 90 after received subcutaneous injection of MWCNTs of 1.0 mg per mouse.
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Carbon nanotubes have been shown to have the ability to transport therapeutic and detective reagents into cells. However, the rapid advances in new carbon nanotube-based materials and technologies have raised concerns about their safety. Such concerns require a fundamental understanding of the toxicological properties of carbon nanotubes. In partic...
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... days after injection, the MWCNTs in the cortex were observably less than at 60 days post-injection, but the aggregates were larger in size (Figure 2b-3). Figure 3 shows representative histological images of sections of the liver, kidney, spleen and heart of mice in the CNT group 2, 7, 30, 60, and 90 days after injection of 1 mg of MWCNTs. For the mice scarified on day 2 post injection MWCNTs, the hepatocytes in the liver were little pale stained swollen with few inflammatory cells and sinusoids were congestion. ...
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... Biofunctionalized CNTs have demonstrated remarkable efficiency as drug carriers for targeted delivery through in vivo studies. Liu et al. [83] showcased successful drug delivery to tumor sites employing biofunctionalized CNTs, resulting in significant tumor growth inhibition while minimizing systemic toxicity [131,132]. The biofunctionalized CNTs Fig. 3 Schematic depicting the usage of bio-functionalized CNTs with a biomolecule or antibody that can recognize the specific cancer cell biomarker to provide a targeted delivery that can inhibit the activity of the cancer cell. ...
The utilization of carbon nanotubes (CNTs) in the field of cancer therapeutics has emerged as a promising avenue of research in recent years. This inquiry delves into the multifaceted potential of bio-functionalized carbon nanotubes for diverse anti-cancer activities. Carbon nanotubes, with their distinct structural and physicochemical properties, offer a versatile platform for innovative approaches in cancer diagnosis, treatment, and comprehension of the underlying molecular mechanisms. The process of bio-functionalizing CNTs plays a pivotal role in enhancing their compatibility with living organisms and specificity, thereby facilitating precise targeting of cancer cells. This scholarly article elucidates the strategies employed for modifying the surface of CNTs and characterizes the bio-functionalized CNTs, setting the stage for their application in anti-cancer therapies. Through a thorough examination of the anti-cancer activities, this research investigates the potential of CNTs to serve as carriers for drug delivery, exemplifying their ability to enhance the availability of drugs and mitigate side effects. Moreover, this study elucidates the diagnostic potential of bio-functionalized CNTs, explicating their applications in cancer imaging, detection, and identification of biomarkers. Mechanistically, the article unveils the pathways through which these nanotubes exert their anti-cancer effects, including the induction of apoptosis and modulation of autophagy. While acknowledging the immense promise of bio-functionalized CNTs, this research also highlights the existing challenges and limitations. Looking toward the future, this article discusses emerging trends in CNT-based cancer therapies, envisioning a future where personalized medicine and nanotechnology converge to revolutionize cancer treatment. Ethical and regulatory considerations are also deliberated upon, emphasizing the need for a responsible and safe transition of these technologies from laboratory experiments to clinical applications. In summary, this study unravels the burgeoning potential of bio-functionalized carbon nanotubes in various anti-cancer activities, underscoring their transformative impact on cancer research and therapy. As the field of nanomedicine continues to expand, these findings contribute to a deeper understanding of the possibilities that lie ahead in the battle against cancer.
Graphical Abstract
... In the present study, the renal tissue of MWCNTs-exposed rats (GP III) displayed multiple histopathological alterations as compared with control rats, like dilatation and congestion of the glomerular capillaries, that concides with the results of Meng et al. (2011).This dilatation might be due to the direct effect of nanoparticles on the endothelial cells of the blood vessels, which might cause the release of the endothelial relaxation factor nitric oxide and vasodilatation (Xia et al., 2006;Gazia and El-Magd, 2019). Moreover, some renal corpuscles displayed shrinkage and degeneration. ...
... The titers of the antibodies after repeated administrations were higher in comparison to those measured after a single inoculum [11]. Immunogenicity is a translational challenge as the production of carrier-specific antibodies has also been reported for various inorganic and synthetic systems; for example, iron oxide NPs, liposomes, multi-walled carbon nanotubes [25][26][27], and obviously other plant viruses [28]. Moreover, the immune response is one of the natural clearance mechanisms, and it does not pose per se any potential health risk or adverse effect. ...
Sonic hedgehog medulloblastoma (SHH-MB) accounts for 25–30% of all MBs, and conventional therapy results in severe long-term side effects. New targeted therapeutic approaches are urgently needed, drawing also on the fields of nanoparticles (NPs). Among these, plant viruses are very promising, and we previously demonstrated that tomato bushy stunt virus (TBSV), functionalized on the surface with CooP peptide, specifically targets MB cells. Here, we tested the hypothesis that TBSV-CooP can specifically deliver a conventional chemotherapeutic drug (i.e., doxorubicin, DOX) to MB in vivo. To this aim, a preclinical study was designed to verify, by histological and molecular methods, if multiple doses of DOX-TBSV-CooP were able to inhibit tumor progression of MB pre-neoplastic lesions, and if a single dose was able to modulate pro-apoptotic/anti-proliferative molecular signaling in full-blown MBs. Our results demonstrate that when DOX is encapsulated in TBSV-CooP, its effects on cell proliferation and cell death are similar to those obtained with a five-fold higher dose of non-encapsulated DOX, both in early and late MB stages. In conclusion, these results confirm that CooP-functionalized TBSV NPs are efficient carriers for the targeted delivery of therapeutics to brain tumors.
... These findings contradicted previous findings when carbon nanotubes were administered intratracheally or intraperitoneally. Hence, these findings showed that administering MWCNTs subcutaneously was safer than administering them systemically [76]. ...
Cancer immunotherapy has made breakthrough progress in cancer treatment. However, only a subset of patients benefits from immunotherapy. Given their unique structure, composition, and interactions with the immune system, carbon nanomaterials have recently attracted tremendous interest in their roles as modulators of antitumor immunity. Here, we focused on the latest advances in the immunological effects of carbon nanomaterials. We also reviewed the current preclinical applications of these materials in cancer therapy. Finally, we discussed the challenges to be overcome before the full potential of carbon nanomaterials can be utilized in cancer therapies to ultimately improve patient outcomes.
... Owing to its nanoscale feature, the presence of MWCNTs in the scaffold matrix mimics the ECM architecture, which suits better than traditional biomaterials in the micro-macro dimensions. Several groups have worked with carbon nanotubes reinforced polymeric scaffolds for neural tissue engineering [20][21][22][23][24][25][26][27][28][29][30][31][32][33]. ...
Electrical stimulation is conducive to neural regeneration. Different types of stimuli propagation patterns are required for regenerating cells in peripheral and central nervous systems. Modulation of the pattern of stimuli propagation cannot be achieved through external means. Reinforcing scaffolds, with suitably shaped conductive second phase materials, is a promising option in this regard. The present study has taken the effort of modulating the pattern (arrangement) of reinforced phase, namely multiwalled carbon nanotubes (MWCNT), in a biodegradable scaffold made of PCL-collagen mixture, by applying an external electric field during curing. Because of their extraordinary physical properties, MWCNTs have been selected as nanoreinforcement for this study. The nature of reinforcement affects the electrical conductivity of the scaffold and also determines the type of cell it can support for regeneration. Further, electrical stimulation, applied during incubation, was observed to have a positive influence on differentiating neural cells in vitro. However, the structure of the nano-reinforcement determined the differentiated morphology of the cells. Reinforced MWCNTs being tubes, imparted bipolarity to the cells. Therefore, these scaffolds, coupled with electrical stimulation possess significant potential to be used for directional regeneration of the nerves.
... Additional in vivo studies revealed that CNT injection leads to activation of the innate immune system and readily initiates the complement cascade [42], inducing the release of radical oxygen species [36,43,44]. Evidence also suggests that MWCNTs is less cytotoxic than their double or single-walled (SWCNT) counterparts [7,45]. ...
This is a proof-of-principle study on the combination of microwaves and multiwalled carbon nanotubes to induce in vivo, localized hyperthermic ablation of cells as a potential methodology for the treatment of localized tumors. Compared to conventional methods, the proposed approach can create higher temperatures in a rapid and localized fashion, under low radiation levels, eliminating some of the unwanted side effects. Following successful ablation of cancer cells in cell culture and zebrafish tumor-xenograft models, it is hypothesized that a cancer treatment can be developed using safe microwave irradiation for selective ablation of tumor cells in vivo using Carbon Nanotube-Antibody (CNT-Ab) conjugates as a targeting agent. In this study, mice were used as an animal model for the optimization of the proposed microwave treatment strategy. The safe dose of CNT-Ab and microwave radiation levels for mice were determined. Further, CNT-Ab distribution and toxicology in mice were qualitatively determined for a time span of two weeks following microwave hyperthermia. The results indicate no toxicity associated with the CNT-Ab in the absence of microwaves. CNTs are only found in the proximity of the site of injection and have been shown to effectively cause hyperthermia induced necrosis upon exposure to microwaves with no noticeable damage to other tissues that are not in direct contact with the CNT-Ab. To understand the cellular immune response towards CNT-Abs, transgenic zebrafish with fluorescently labeled macrophages and neutrophils were used to assay for their ability to phagocytize CNT-Ab. Our results indicate that macrophages and neutrophils were able to actively phagocytose CNT-Abs shortly after injection. Taken together, this is the first study to show that CNTs can be used in combination with microwaves to cause targeted ablation of cells in mice without any side effects, which would be ideal for cancer therapies.
... However, functionalised CNTs could still exert dose−dependent cytotoxic effects. post injection, however, the cytokine levels returned to normal 7 days post injection [72]. ...
Tumour−specific, immuno−based therapeutic interventions can be considered as safe and effective approaches for cancer therapy. Exploitation of nano−vaccinology to intensify the cancer vaccine potency may overcome the need for administration of high vaccine doses or additional adjuvants and therefore could be a more efficient approach. Carbon nanotube (CNT) can be described as carbon sheet(s) rolled up into a cylinder that is nanometers wide and nanometers to micrometers long. Stemming from the observed capacities of CNTs to enter various types of cells via diversified mechanisms utilising energy−dependent and/or passive routes of cell uptake, the use of CNTs for the delivery of therapeutic agents has drawn increasing interests over the last decade. Here we review the previous studies that demonstrated the possible benefits of these cylindrical nano−vectors as cancer vaccine delivery systems as well as the obstacles their clinical application is facing.
... Nevertheless, we believe it is important to test for these events routinely for any type of iNP-injection based on the observations that platelet aggregation and complement activation can be observed after s.c. (Ermidou-Pollet et al. 2005) and i.m (Atkinson, Taylor, and Chetty 1985) injections of nanomaterials (Meng et al. 2011). Moreover, hemolysis has been reported to occur after i.m. diclofenac-therapy as well (Ahrens et al. 2004). ...
The increasing nanomedicine usage has raised concerns about their possible impact on human health. Present evaluation strategies for nanomaterials rely on a case-by-case hazard assessment. They take into account material properties, biological interactions, and toxicological responses. Authorities have also emphasized that exposure route and intended use should be considered in the safety assessment of nanotherapeutics. In contrast to an individual assessment of nanomaterial hazards, we propose in the present work a novel and unique evaluation strategy designed to uncover potential adverse effects of such materials. We specifically focus on spherical engineered nanoparticles used as parenterally administered nanomedicines. Standardized assay protocols from the US Nanotechnology Characterization Laboratory as well as the EU Nanomedicine Characterisation Laboratory can be used for experimental data generation. We focus on both cellular uptake and intracellular persistence as main indicators for nanoparticle hazard potentials. Based on existing regulatory specifications defined by authorities such as the European Medicines Agency and the United States Food and Drug Administration, we provide a robust framework for application-oriented classification paired with intuitive decision making. The Hazard Evaluation Strategy (HES) for injectable nanoparticles is a three-tiered concept covering physicochemical characterization, nanoparticle (bio)interactions, and hazard assessment. It is cost-effective and can assist in the design and optimization of nanoparticles intended for therapeutic use. Furthermore, this concept is designed to be adaptable for alternative exposure and application scenarios. To the knowledge of the authors, the HES is unique in its methodology based on exclusion criteria. It is the first hazard evaluation strategy designed for nanotherapeutics.
... The c-MWCNTs were developed from the pristine MWCNTs (p-MWCNTs). The p-MWCNTs were purchased from Chengdu Organic Chemicals Co. Ltd. (Chengdu, China) and the c-MWCNTs were prepared as previously described 41 . In brief, the c-MWCNTs were synthesized based on the p-MWCNTs through a combined oxidation procedure and probe sonication. ...
The impact of nanomaterials on immune cells is gaining attention but is not well documented. Here, we report a novel stimulating effect of carboxylated multi-walled carbon nanotubes (c-MWCNTs) on the migration of macrophages and uncover the underlying mechanisms, especially the upstream signaling, using a series of techniques including transwell migration assay, patch clamp, ELISA and confocal microscopy. c-MWCNTs dramatically stimulated the migration of RAW264.7 macrophages when endocytosed, and this effect was abolished by inhibiting phospholipase C (PLC) with U-73122, antagonizing the IP3 receptor with 2-APB, and blocking calcium release-activated calcium (CRAC) channels with SK&F96365. c-MWCNTs directly activated PLC and increased the IP3 level and [Ca²⁺]i level in RAW264.7 cells, promoted the translocation of the ER-resident stromal interaction molecule 1 (STIM1) towards the membranous calcium release-activated calcium channel modulator 1 (Orai1), and increased CRAC current densities in both RAW264.7 cells and HEK293 cells stably expressing the CRAC channel subunits Orai1 and STIM1. c-MWCNTs also induced dramatic spatial polarization of KCa3.1 channels in the RAW264.7 cells. We conclude that c-MWCNT is an activator of PLC and strongly recruits macrophages via the PLC/IP3/CRAC channel signaling cascade. These novel findings may provide a fundamental basis for the impact of MWCNTs on the immune system.
... Their results demonstrated that the PVA-MWCNT scaffold can improve functional recovery and myelination of the regenerated nerve fibers without eliciting inflammation degeneration in all internal organs. On the other side, there are also some potential toxic concerns with use of CNTs as scaffold or drug delivery platforms [24][25][26][27]. For instance, one study by Meng et al reported that CNTs can migrate from subcutaneous implants to regional lymph nodes, slightly eliciting inflammatory cytokine levels [27]. ...
... On the other side, there are also some potential toxic concerns with use of CNTs as scaffold or drug delivery platforms [24][25][26][27]. For instance, one study by Meng et al reported that CNTs can migrate from subcutaneous implants to regional lymph nodes, slightly eliciting inflammatory cytokine levels [27]. However, inflammatory cytokine levels returned to their original level within three months after injection of MWCNTs. ...
Objective:
Nanomaterials, such as carbon nanotubes (CNTs), have been introduced to modify the surface properties of scaffolds, thus enhancing the interaction between the neural cells and biomaterials. In addition to superior electrical conductivity, CNTs can provide nanoscale structures similar to those present in the natural neural environment. The primary objective of this study is to investigate the proliferative capability and differential potential of neural stem cells (NSCs) seeded on a CNT incorporated scaffold.
Approach:
Amine functionalized multi-walled carbon nanotubes (MWCNTs) were incorporated with a PEGDA polymer to provide enhanced electrical properties as well as nanofeatures on the surface of the scaffold. A stereolithography 3D printer was employed to fabricate a well-dispersed MWCNT-hydrogel composite neural scaffold with a tunable porous structure. 3D printing allows easy fabrication of complex 3D scaffolds with extremely intricate microarchitectures and controlled porosity.
Main results:
Our results showed that MWCNT-incorporated scaffolds promoted neural stem cell proliferation and early neuronal differentiation when compared to those scaffolds without the MWCNTs. Furthermore, biphasic pulse stimulation with 500 µA current promoted neuronal maturity quantified through protein expression analysis by quantitative polymerase chain reaction.
Significance:
Results of this study demonstrated that an electroconductive MWCNT scaffold, coupled with electrical stimulation, may have a synergistic effect on promoting neurite outgrowth for therapeutic application in nerve regeneration.
