Stimuli-Responsive Poly(Disulfide)s: A Versatile Platform for Intelligent Drug Delivery Systems

Abstract

Poly(disulfide)s represent a class of dynamic polymers whose synthesis is facilitated by the reversible exchange and recombination of disulfide bonds. This unique polymerization mechanism, combined with the structural flexibility of cyclic disulfide monomers and the diversity of ring-opening polymerization (ROP) methods, enables precise control over polymer architecture and functionality. The resulting materials exhibit remarkable characteristics including reversible redox-responsiveness, tunable degradation kinetics, self-healing capabilities, and enhanced cellular uptake efficiency. This review systematically examines the fundamental aspects of poly(disulfide)s, beginning with the design principles of monomer structures and progressing through various ROP strategies such as thermal, photo-initiated, and catalyst-mediated approaches. We critically analyze how these synthetic parameters influence key polymer properties including molecular weight distribution, stimulus responsiveness, and biocompatibility. The application potential of poly(disulfide)s in drug delivery is comprehensively explored, with particular focus on their performance in nucleic acid delivery systems for gene therapy, protein and peptide delivery for biotherapeutic applications, and small molecule drug carriers for enhanced therapeutic efficacy. By integrating recent advances in polymer chemistry with biomedical engineering perspectives, this review aims to provide valuable insights for the rational design of poly(disulfide)-based delivery platforms and their translation into clinical applications.