Glucose oxidase and conjugated polymer nanocomplexes for synergistic photothermal/starvation/oxidation therapy

Abstract

Photothermal therapy (PTT) is becoming a prevalent tumor therapeutic method, but the overexpression of heat shock proteins (HSPs) and the self-repair mechanism of malignant tumors may restrict its therapeutic effect. Glucose oxidase (GOx) has been reported to effectively block the uptake of nutrients by tumor cells via starvation therapy, further debasing the production of HSPs in cells. Thus motivated, a nanoplatform (IBDDP&GOx NPs) integrating PTT, starvation therapy and oxidation therapy was constructed using a near-infrared BODIPY-based conjugated polymer (IBDDP) and GOx. Through the electrostatic interaction between the positively charged imidazole group from IBDDP and the negatively charged GOx, IBDDP and GOx could assemble into stable nanocomplexes, simultaneously solving the problem of insolubility of BODIPY-based conjugated polymers in aqueous solution as well as the poor stability and grievous system toxicity of GOx. Additionally, IBDDP&GOx NPs effectively retain the excellent photothermal properties of IBDDP and the biological catalytic activity of GOx, thus exhibiting enhanced inhibitory effects on tumor cell survival and malignant proliferation. This work proposed a simple example of integrating conjugated polymers with functional proteins into one formulation, which could overcome the shortcomings of single therapy and achieve a better synergistic treatment effect by multimodal cancer therapy.