Oxygen- and bubble-generating polymersomes for tumor-targeted and enhanced photothermal–photodynamic combination therapy

Abstract

As a common feature of the tumor microenvironment (TME), hypoxia significantly impedes the effects of photodynamic therapy. Moreover, for tumor combination therapy, smart responsive and well-designed nanocarriers are highlighted to co-deliver different therapeutics, enhance drug delivery into target sites, and realize stimuli-responsive drug release. Herein, oxygen- and bubble-generating polymersomes (FIMPs) were developed for tumor-targeted and enhanced photothermal–photodynamic combination therapy. FIMPs efficiently co-encapsulated manganese dioxide (MnO₂) and the hydrophobic photosensitizer indocyanine green (ICG) within the hydrophobic membrane as well as the bubble-generating reagent NH₄HCO₃ in the internal cavity of the vesicles, and achieved pH/temperature/reduction multiple responsiveness. The CO₂ bubbles generated from the decomposition of NH₄HCO₃via laser irradiation or acidic environment and the cleavage of the copolymer disulfide bond in the reducing TME would destroy the vesicle structure for triggering drug release. In addition, oxygen can be produced to overcome tumor hypoxia through the high reaction activity of MnO₂ with endogenous H₂O₂. In vitro studies have shown that FIMPs achieved good photothermal conversion efficiency, promoted the generation of oxygen and reactive oxygen species (ROS), and thus effectively killed tumor cells. In vivo studies indicated that FIMPs effectively overcome the hypoxic microenvironment within tumors and significantly inhibit tumor growth with good biocompatibility. The rationally designed oxygen- and bubble-generating polymersomes have great potential to overcome the tumor hypoxia limitations for enhancing the photothermal–photodynamic combination therapeutic effect.