Amphiphilic poly(disulfide)s by a three-component Cascade reactions: a therapeutic architecture for redox-responsive intracellular drug delivery

We reported a new cascade type of synthetic methodology for poly(disulfide)s (PDS) from lipoic acid-based monomer. The primary amine-based activator and thiolactone initiator was used for the synthesis of poly(disulfide)s by ring opening disulfide exchange polymerization (RODEP) technique. This methodology offers <i>in situ</i> dual functionalization in the polymer chain end to synthesize a functional poly(disulfide)s. It was found to form a stable nanocarrier in aqueous medium with size of 100 nm by entropically driven pathway. It showed very low critical aggregation concentration and high encapsulation stability. Next, the degradation of the polymer chains in presence of glutathione was probed by chromatographic technique, which shows complete degradation of polymer chains. The GSH triggered guest release of PDS nanocarrier revealed almost ∼84% release in a controlled fashion. The MTT assay indicated excellent biocompatibility of the polymer itself as more than 90% cells were alive after 24 h of incubation of the polymer against HeLa cells. The cytotoxicity of the PDS@DOX exhibited more than 70% of cell death in 24 h of incubation. The live cell fluorescence microscopy studies revealed time dependent cellular internalization of the PDS@DOX, which supported the cancer cell death due to doxorubicin internalization followed by diffusion to the nucleus.