pH-degradable and thermoresponsive water-soluble core cross-linked polymeric nanoparticles as potential drug delivery vehicle for doxorubicin†
Controlled and efficient delivery of therapeutics to tumor cells is one of the key issues in cancer therapy. In the present work, a new class of water soluble core cross-linked polymer nanoparticles (CLPNs) possessing acid degradable core and thermoresponsive shell was synthesized for pH-triggered delivery of drugs to cancerous cells. The diol groups of the poly(ethylene glycol)-b-poly(N-isopropylacrylamide)-b-poly(glycidyl methacrylate) diol triblock copolymer were utilized to form the core cross-linked polymeric nanoparticles through an arm-first method by reaction with aldehyde functionalized cross-linkers through formation of acetal linkages. The encapsulation efficiency as well as the release properties of these CLPNs was investigated using doxorubicin (DOX), a known anticancer drug. The release was found to be preferable at the desired lysosomal pH (∼5.0) of the cancer cells and below the LCST (∼32 °C) of poly(N-isopropylacrylamide) (PNIPA). The cytotoxicities of the precursor polymer as well as the CLPNs were tested on the growth of NIH/3T3, normal mouse fibroblast cells, and they were found to be nontoxic. The anticancer activity of the DOX loaded CLPN was confirmed using cervical cancer cell lines HeLa and SiHa by MTT assay, morphological studies and flow cytometry. These studies revealed an increased accumulation of the drug around the nucleus when treated with DOX-loaded CLPN as compared to free DOX along with significant reduction in IC50 of both the cell lines. Thus, these CLPNs are potentially useful for controlled drug delivery in the case of advanced chemotherapeutic applications.