Dual-responsive amphiphilic cysteine block copolypeptide: self-assembled vesicles for dye encapsulation and photo-triggered release†

Abstract

The inherent biocompatibility and biodegradability of functionalized smart polypeptides make them attractive for biomedical applications, including drug delivery and tissue engineering. Inspired by this prospect, herein, we report a dual stimuli-responsive amphiphilic block copolypeptide, [(PCys-g-PNIPAM)-b-(PCys-NB)], which exhibits both thermo- and photo-responsiveness in aqueous media. The copolypeptide is synthesized via a multi-step reaction starting from thiol-mediated radical polymerization of N-isopropylacrylamide (NIPAM) to cysteine-terminated PNIPAM (Cys-PNIPAM) for subsequent cyclization to the corresponding N-carboxyanhydride (Cys-PNIPAM NCA). Ring-opening polymerization (ROP) of this NCA produces a PCys-g-PNIPAM block, which serves as a macroinitiator for the ROP of 2-nitrobenzyl-functionalized cysteine NCA (Cys-NB NCA), forming the targeted copolypeptide. The grafted PNIPAM segments impart tunable lower critical solution temperature (LCST)-type reversible phase behaviour in water. Upon UV irradiation (λ = 350 nm), the photocleavage of the nitrobenzyl groups transforms PCys-NB into PCys-COOH, increasing the hydrophilicity of the copolypeptide and increasing its cloud point. In aqueous solution, the copolypeptide self-assembles into vesicular nanostructures capable of encapsulating a hydrophobic dye. The UV-induced cleavage of the NB moiety disrupts the vesicular structures due to an imbalance in the hydrophilic–hydrophobic ratio of the formed copolypeptide, resulting in triggered release of the encapsulated dye. The temperature-controlled encapsulation efficiency and light-triggered release of cargo highlights the potential of this block copolypeptide as a dual-responsive carrier for smart drug delivery application.