Combinatorial delivery of superparamagnetic iron oxide nanoparticles (γFe2O3) and doxorubicin using folate conjugated redox sensitive multiblock polymeric nanocarriers for enhancing the chemotherapeutic efficacy in cancer cells

Redox sensitive, folate conjugated multiblock polymeric system of (-PLGA-PEG-PLGA-urethane-ss-) demonstrated self-assembly into stable nanoplatforms. The polymeric nanocarriers were encapsulated with doxorubicin and highly crystalline γFe2O3 superparamagnetic iron oxide nanoparticles (SPIONs), for co˗delivery of the same to cancer cells, with average particle size of ~170nm and zeta potential of ~−33mV. Furthermore, the designed formulation was evaluated for protein adsorption, hemo˗cytocompatibility and stability. Glutathione (GSH) induced redox sensitivity of the nanocarriers was depicted by ~4.47 fold increase in drug release in the presence of 10mM 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. [Display omitted] •Combined delivery of γFe2O3 nanoparticles and doxorubicin through targeted nanocarriers is proposed.•Biocompatible and biodegradable, redox sensitive multiblock copolymer is developed and explored for the study.•Nanoparticles have enhanced cellular uptake in folate overexpressing cell lines, HeLa and MDA-MB-231.•Combinatorial delivery shows synergistic effect of radiofrequency induced hyperthermia and chemotherapy in cancer cells.