Amphiphilic block copolymer poly(2-methacryloyloxyethyl phosphorylcholine) and poly(trimethylene carbonate): Preparation and for intracellular drug delivery

A robust redox-responsive block copolymer was proposed and prepared as drug vehicle based on disulfide linked poly(2-methacryloyloxyethyl phosphorylcholine) and poly(trimethylene carbonate) (PMPC-ss-PTMC). The size and morphology of the polymer nanoparticles were characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The profile of drug release response to glutathione (GSH) was monitored in vitro. Upon 10 mM GSH, mimicking the intracellular microenvironments such as cytosol and the cell nucleus, the resulted drug carrier was destructed ascribe to abruption of the disulfide bonds, followed by accelerated drug release from the nanoparticles. MTT assay showed that the blank micelles did not reveal cytotoxicity to the human cervical cancer HeLa cells and mouse connective tissue fibroblast L929 cells even up to 500 μg/mL. On the other hand, the Doxorubicin-loaded (DOX-loaded) micelles that contained disulfide bonds exhibit a higher cytotoxicity against HeLa cells than that of no disulfide bonds, but there was no significant difference in cytotoxicity against the L929 cells. Confocal laser scanning microscopy and flow cytometry investigation showed that the DOX-loaded micelles can be swiftly internalized, and effectively transmitted the drugs into nuclei. These results suggested that the copolymer as a robust and effective redox-responsive nanocarrier to augment drug efficacy for cancer cells.