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 .
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 . 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 .
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 . 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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