Cytotoxicity of Gold Nanoparticles
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Cytotoxicity of Gold Nanoparticles: A Comprehensive Overview
Introduction to Gold Nanoparticles and Cytotoxicity
Gold nanoparticles (AuNPs) have garnered significant attention in various fields, including biomedical imaging, diagnostics, and therapeutic applications, due to their unique properties and chemical stability. However, the cytotoxicity of AuNPs remains a topic of debate, with studies showing varying results based on different parameters such as size, shape, surface chemistry, and the biological environment Pan2007Kus-Liśkiewicz2021.
Size-Dependent Cytotoxicity of Gold Nanoparticles
The size of gold nanoparticles plays a crucial role in determining their cytotoxic effects. Studies have shown that smaller AuNPs, particularly those around 1.4 nm in diameter, exhibit higher cytotoxicity compared to larger particles. These smaller particles tend to induce rapid cell death through necrosis, while slightly larger particles (1.2 nm) primarily cause apoptosis Pan2007Pan2009. In contrast, larger AuNPs (e.g., 15 nm) are generally non-toxic even at higher concentrations .
Shape and Surface Chemistry Influence on Cytotoxicity
The shape and surface chemistry of AuNPs also significantly impact their cytotoxicity. For instance, gold nanorods have been found to be more cytotoxic than nanostars and nanospheres, likely due to differences in cellular uptake and interaction with cellular components . Additionally, the presence of surface contaminants, such as sodium citrate residues, can impair cell viability and increase cytotoxicity . The surface capping agents and ligand chemistry, such as triphenylphosphine monosulfonate (TPPMS) or glutathione, also modulate the degree of cytotoxicity by influencing oxidative stress and mitochondrial damage Pan2009Deng2017.
Cellular Uptake and Mechanisms of Cytotoxicity
The internalization of AuNPs by cells is a critical factor in their cytotoxic effects. Studies have shown that AuNPs are internalized through endocytosis and accumulate in membrane-bound vesicles within cells . The cytotoxicity of AuNPs is often associated with the generation of reactive oxygen species (ROS), leading to oxidative stress, mitochondrial damage, and activation of apoptosis or necrosis pathways Pan2009Ibrahim2023. The inhibition of the ubiquitin proteasome system (UPS) by AuNPs further contributes to cytotoxicity by triggering mitochondrial-related apoptosis .
Differential Cytotoxic Effects in Various Cell Lines
The cytotoxic effects of AuNPs can vary significantly across different cell lines. For example, Vero cells exhibit apoptosis upon exposure to AuNPs, while MRC-5 and NIH3T3 cells do not show the same response . This differential cytotoxicity is linked to various cellular processes, including DNA damage, cell-cycle regulation, and oxidative stress responses . Additionally, the cytotoxicity of AuNPs can be modulated by the presence of a biological corona formed by serum proteins, which affects their interaction with cells .
Potential Therapeutic Applications and Safety Considerations
Despite their cytotoxic potential, AuNPs hold promise for therapeutic applications, particularly in cancer treatment. At non-cytotoxic concentrations, AuNPs can impair metastasis hallmarks and weaken tumor cells, making them potential antitumor agents . However, the lack of standardized safety regulations and reliable methodologies for assessing AuNP toxicity remains a significant challenge . It is crucial to establish specific and universal protocols for characterizing the safety and biocompatibility of AuNPs to advance their application in healthcare.
Conclusion
The cytotoxicity of gold nanoparticles is a complex phenomenon influenced by multiple factors, including size, shape, surface chemistry, and the biological environment. While smaller AuNPs and certain shapes exhibit higher cytotoxicity, larger particles and specific surface modifications can mitigate these effects. Understanding these parameters is essential for developing safe and effective AuNP-based applications in biomedicine. Future research should focus on standardizing safety assessments and exploring the therapeutic potential of AuNPs at non-cytotoxic concentrations.
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Biocompatibility and Cytotoxicity of Gold Nanoparticles: Recent Advances in Methodologies and Regulations
Gold nanoparticles' biocompatibility and cytotoxicity depend on their intrinsic characteristics, biological target, and evaluation methodology, and standardization of safety regulations is needed for their widespread use in healthcare.
Differential cytotoxic effects of gold nanoparticles in different mammalian cell lines.
Gold nanoparticles show varying cytotoxic effects in various mammalian cell lines, with apoptosis induction in Vero cells and apoptosis induction in MRC-5 and NIH3T3 cells.
Gold nanoparticles of diameter 1.4 nm trigger necrosis by oxidative stress and mitochondrial damage.
Gold nanoparticles of diameter 1.4 nm capped with TPPMS cause necrosis by oxidative stress and mitochondrial damage, with reducing agents/antioxidants reducing toxicity.
Gold nanoparticles induce cytotoxicity in the alveolar type-II cell lines A549 and NCIH441
The presence of sodium citrate residues on gold nanoparticles can cause cytotoxicity in vitro, but does not influence the uptake of the particles in human alveolar type-II-like cell lines.
Shape-dependent cytotoxicity and cellular uptake of gold nanoparticles synthesized using green tea extract
Gold nanoparticles with nanorods having the highest cytotoxicity and nanostars having the highest cellular uptake show potential for therapeutic applications in nanomedicine.
Beyond gold nanoparticles cytotoxicity: potential to impair metastasis hallmarks.
GA-AuNPs, stabilized by gum arabic, can effectively inhibit melanoma cell invasion and growth, while avoiding cytotoxicity and maintaining desirable antitumor effects.
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