Nucleus-Targeted Delivery of Anticancer Drug Using Alpha-Synuclein(Y136C)-Gold Nanoparticle Conjugates

The nucleus plays a central role in eukaryotic cell survival by regulating essential processes. This makes it a strategic target for disrupting tumor growth in cancer therapy. Conventional nucleus-directed anticancer agents, including doxorubicin (Dox), have demonstrated effectiveness in treatment but face challenges related to poor cellular uptake and nuclear localization. To overcome these limitations, nanoparticle-based systems have been explored. In this study, α-synuclein-gold nanoparticle conjugates (αS-AuNPs) were employed as an intracellular drug delivery system for nuclear-targeted cancer therapy. αS, an intrinsically disordered protein, facilitates cellular uptake and nuclear accumulation. Dox was linked to αS-(Y136C)-AuNP via a heat-labile cross-linker, enabling controlled drug release upon near-infrared (NIR) irradiation. The photothermal effect of AuNPs induced localized hyp…