Combinatorial delivery of superparamagnetic iron oxide nanoparticles(γFe_2O_3) and doxorubicin using folate conjugated redox sensitive multiblock polymeric nanocarriers for enhancing the chemotherapeutic efficacy in cancer cells

摘要

Redox sensitive, folate conjugated multiblock polymeric system of (-PLGA-PEG-PLGA-urethane-ss-) demonstrat¬ ed self-assembly into stable nanoplatforms. The polymeric nanocarriers were encapsulated with doxorubicin and highly crystalline γFe_2O_3 superparamagnetic iron oxide nanoparticles (SPIONs), for co-delivery of the same to cancer cells, with average particle size of-170 nm and zeta potential of ～-33 mV. Furthermore， the designed formulation was evaluated for protein adsorption, hemo-cytocompatibility and stability. Glutathione (GSH) in¬ duced redox sensitivity of the nanocarriers was depicted by ~4.47 fold increase in drug release in the presence of 10 mM GSH. In vitro cellular uptake studies of the designed nanocarriers showed synergistic cytotoxic effect in folate overexpressing cells (HeLa and MDA-MB-231), after subjecting the cells to radio frequency (RF) induced hyperthermia （~43 °C）. Negligible effect of the combinatorial therapy was observed in normal cells (L929). The developed polymeric system depicted facile synthesis, reproducibility and potential for achieving combinatorial and targeted delivery of drug and SPIONs to cancer cells. This combinatorial approach can help in achieving better therapeutic effect with minimal side effects of chemotherapy.