Redox-Sensitive Core Cross-Linked Polyethylene Glycol-Polypeptide Hybrid Micelles for Anticancer Drug Delivery

Abstract

A novel redox-sensitvie core cross-linked micelles based on disulfide-linked PEG-polypeptide hybrid polymer were prepared and demonstrated for anticancer drug delivery, where N,N-bis(acrylate) cystamine (BAC) served as cross-linker, allyl-terminated poly(γ-benzyl-L-glutamate) (PBLG) and polyethylene glycol (PEG) methyl ether methacrylate acted as comonomers. The molecular structure and characteristics of the cross-linked micelle and the precursor were confirmed by 1H NMR and FT-IR. The cross-linked micelles could be easily degraded into individual linear short chains (Mn = 1800) in the presence of 20 mM glutathione (GSH) by the cleavage of the disulfide linkages from the cross-linker BAC. Doxorubicin (DOX) was selected as a model anticancer drug and encapsulated into the micelles with a decent drug loading content of 21.6 wt%. Compared to the burst release of free DOX in first 6 hours, the in vitro release studies revealed that the micelles exhibited a sustained and high cumulative drug release in GSH (up to 86%) within 24 h, rather than the relatively low release rate of 62% in PBS (pH 7.4). Cell cytoxicity experiments showed that the obtained micelles exhibited nontoxic, and the drug-loaded micelles exhibited high anti-cancer efficacy. All the results showed that the designed cross-linked PEG-polypeptide hybrid micelles may be a promising vehicle for anticancer drug delivery with stimuli-triggered drug release behavior in reducing environment.