Flash dissolving nanofiber membranes for chemo/cascade chemodynamic therapy of oral cancer

Abstract

Cellular glucose and glutathione (GSH)-responsive nanofiber (NF) membrane system was developed for combined chemo/cascade chemodynamic therapy. Glucose oxidase (GOx), MnO2, and rapamycin were encapsulated in polyvinyl alcohol (PVA) NF for glucose decomposition/H2O2 generation, OH radical production based on Fenton-like reaction/GSH depletion/O2-induced hypoxia relief, and antiproliferation in cancer therapy, respectively. Restriction in the physicochemical properties of drug cargos, such as lower dispersibility of MnO2 and lower solubility of rapamycin in water, was overcome with the electrospinning process and homogeneous NF membrane was successfully fabricated. Designed NF mat structure exhibited immediate wetting, disintegrating, and drug releasing characteristics, which can be ideal requisites for oral cavity administration. In oral cancer cells (YD-9 cells), GOx in NF mat decomposed highly accumulated glucose to H2O2. MnO2 reduced cellular GSH level in cancer cells and generated O2 for hypoxia relief, in addition, Mn2+ successfully transformed H2O2 into OH radical. With these cascade catalytic reaction strategies, incorporated rapamycin in NF mat had an antiproliferation potential in oral cancer cells. Combination effects between GOx/MnO2 and rapamycin entrapped in NF mat were also demonstrated in 3D-cultured YD-9 tumor spheroid model. Designed PVA/GOx/MnO2/rapamycin NF mat can be used safely and conveniently as an anticancer drug delivery platform.