Redox-sensitive shell cross-linked PEG–polypeptide hybrid micelles for controlled drug release

Novel PEG–polypeptide hybrid drug carriers, poly(ethylene glycol)-b-poly(L-cysteine)-b-poly(L-phenylalanine) (PEG-PCys-PPhe) triblock copolymers, were prepared via the ring-opening polymerization of amino acid N-carboxyanhydrides. The copolymers can self-assemble to form core–shell–corona micelles in aqueous solutions. The shell of the micelles has the ability to self-cross-link (SCL) by the oxidation of thiol groups in the PCys segments. The morphology and stability of SCL micelles were characterized by TEM, DLS and SEM. The results showed the SCL micelles could hold the physical structure of micelles in severe environments. The in vitro drug release in response to GSH was also studied. It was found that the cross-linked shell could be helpful to reduce the drug loss in the extracellular environment. Under a reductive environment, the micelles would undergo the destruction of the cross-linked shell due to the cleavage of disulfide bonds, followed by accelerated drug release from the micelles. The glutathione-responsive SCL micelles could be easily uptaken by HeLa cells, suggesting these micelles might have great potential in intracellular drug delivery.