Owing to the straightforward synthesis, good biological compatibility, and ease of surface functionalization, gold nanoparticles (AuNPs) have shown great potential in various biomedical applications, including diagnostic imaging, photothermal therapy (PTT), and drug delivery. Physicochemical properties (e.g. shape, size and surface chemistry) may potentially affect the interaction of AuNPs with biological systems, thus ultimately influencing their cell uptake, pharmacokinetics, biodistribution, drug delivery efficiency, and biological effects. This review focuses on recent advances in understanding the relation between physicochemical characteristics of AuNPs and their navigation through different biological processes, including biodistribution, penetration of biological barriers (e.g. blood-brain barrier), clearance, and metabolism. Furthermore, the in vitro and in vivo toxicological effects of AuNPs and their possible mechanisms were discussed. A thorough understanding of these influencing factors will be crucial for the rational design, customized functionalization, and clinical translation of AuNPs in drug delivery.
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