Stainless Steel-Synthesized gold Nanoparticles: Insights into Blood-Brain barrier permeability and microglial...

Effective drug delivery to the Central Nervous System (CNS) remains a formidable challenge in neurotherapeutics, primarily due to the restrictive Blood-Brain Barrier (BBB). Gold nanoparticles (AuNPs) are emerging as promising tools to bypass this barrier and manage neuroinflammation, key factor in numerous neurological disorders. In this work, we evaluate the potential of highly stable, small-sized AuNPs-synthesized via an environmentally benign method using stainless steel-as a dual-function nanocarrier system for CNS applications. We specifically investigate their capacity for BBB permeability using in vitro models and their subsequent interaction with resident immune cells (microglia), which is critical for safety and efficacy. We demonstrate that stainless steel-synthesized AuNPs (ss-AuNPs) effectively cross the barrier without compromising its integrity. In microglial cells, ss-AuNPs exhibited dose-dependent cytotoxic effects, with higher concentrations reducing cell viability while inducing minimal inflammatory responses. Similarly, in primary microglial cultures, ss-AuNPs at higher doses stimulated interleukin-6 (IL-6) release, although no significant pro-inflammatory activation was observed at lower doses. These results highlight the potential of green-synthesized AuNPs for CNS-targeted applications, validating their promise as stable and safe nanocarriers for future drug formulation targeting neurological diseases.