Silver Nanoparticles and Neurotoxicity: Mechanistic Insights and Recent Experimental Evidence

Silver nanoparticles (AgNPs) have gained significant interest across various areas arising from their multifunctional mechanisms. Biomedical applications are one of the areas where the therapeutic and diagnostic potential of AgNPs are highlighted. Considering the expansion of biomedical use of AgNPs, nervous system-based applications, including neuroimaging, neural implant coatings and development of neural tissue-targeted drug delivery systems are some of the potential applications of AgNPs in the current research. However, growing interest in these nervous system related applications and the limited regenerative capacity of neural tissues make it essential to carefully evaluate the potential neurotoxic effects of AgNPs. AgNP-induced responses in neural tissues may differ according to key physicochemical and exposure-related parameters, specifically particle size, shape, surface chemistry, coating properties, protein corona formation, exposure route, dose, and duration. Among the possible mechanisms that may contribute to these responses are blood-brain barrier (BBB) disruption, mitochondrial dysfunction and oxidative stress, neuroinflammation and glial activation, and cell death processes such as apoptosis, autophagy, and ferroptosis. In this review, in the context of the potential neurotoxic effects of AgNPs on the nervous system, the main parameters that determine AgNP neurotoxicity and the possible mechanisms involved are examined in detail, where recent scientific developments in this field are evaluated based on current in vitro and in vivo studies.