Harnessing Sulfur Chemistry: Functional Groups as Key Drivers for Advanced Therapeutic Nanodelivery

Sulfur-containing nanocarriers have emerged as highly versatile platforms for therapeutic delivery owing to their distinct physicochemical and redox-responsive properties. Sulfur-containing groups, ranging from simple sulfides to complex thioketals, are versatile tools in nanocarrier engineering. Their incorporation not only modulates structural stability and uptake but also enables precise drug release and organ-selective accumulation. Despite these advantages, several challenges hinder their broader translation. The difficulties of precisely tuning sulfur-motif interconversion, maintaining redox stability under complex in vivo conditions, and achieving consistent clinical benefit across diverse disease contexts are still needed to be addressed. This review synthesizes current knowledge on the structural features, mechanistic underpinnings, and functional roles of sulfur-modified delivery systems in overcoming major drug-delivery barriers. We highlight recent advances in sulfur-enabled nanoplatforms for targeted and stimuli-responsive therapies. Also, we introduce a classification framework that organizes sulfur-containing carriers according to their redox-active motifs. By elucidating how oxidation–reduction dynamics dictate cargo release and therapeutic performance, we provide a foundation for rational design of next-generation sulfur-based delivery technologies. Finally, we discuss existing limitations and outline key research directions needed to advance the clinical translation of sulfur-driven nanodelivery strategies.