Reduction-responsive cross-linked micelles based on PEGylated polypeptides prepared via click chemistry

This study aims to develop novel reduction-responsive cross-linked micelles (CMs) based on poly(ethylene glycol)-block-poly(gamma-propargyl-L-glutamate) (PEG-PPLG) by click chemistry. H-1 NMR spectroscopy, IR spectroscopy, dynamic light scattering (DLS) and transmission electron microscopy (TEM) were performed to confirm the successful construction of the CMs. Doxorubicin (DOX) was loaded into the CMs as a model anticancer drug. The DOX-loaded CMs could hold the drug under physiological conditions, and release the payload quickly in the presence of glutathione (GSH). Confocal laser scanning microscopy (CLSM) and flow cytometry measurements revealed that the intracellular drug release from the DOX-loaded CMs was increased in the HeLa cells with an enhanced intracellular GSH level. In vitro methyl thiazolyl tetrazolium (MTT) assays indicated that the CMs were biocompatible, and DOX-loaded CMs showed higher cellular proliferation inhibition towards GSH-pretreated HeLa cells than non-pretreated cells. Due to their unique responsiveness, the biocompatible CMs show promise for the intracellular delivery of chemotherapeutic drugs in cancer therapy.