Tumor microenvironment/NIR-responsive oxygen-irrelevant radical nanogenerator for hypoxia-independent photothermal-thermodynamic osteosarcoma nanotherapy

Abstract

Although photothermal therapy (PTT) have aroused substantial attention in the treatment of various types of tumors, the antitumor therapeutic efficacy is still unsatisfactory when using PTT alone. Very recently, oxygen-independent free-radical generation based on thermodynamic therapy (TDT) has emerged as a potential powerful therapeutic strategy for hypoxic cancer therapy. Herein, in this work, an intelligent hypoxia-independent free radical nanogenerator (CuS/AIPH@MnO2, denoted as CAM) was fabricated by in situ coating manganese dioxide (MnO2) shell onto the surface of as 2,2-azobis[2-(2-imidazolin-2-yl) propane] dihydrochloride (AIPH)-loaded mesoporous hollow mesoporous copper sulfide (CuS). The local hyperthermal generated by CAM upon NIR laser irradiation not only permitted PTT, but also promoted the disintegration of AIPH for generation of oxygen-independent free radicals, exerting the advantages of combination therapy of PTT/TDT for effective tumor ablation. Simultaneously, both in vitro and in vivo results have demonstrated the synergistic therapeutic efficacy of PTT/TDT for remarkable tumor growth inhibition. In addition, the favorable biocompatibility and low cytotoxicity of the as-synthesized nanoparticles were verified both in vitro and in vivo. Collectively, this work proposed an attractive and promising strategy in cancer therapy based on generation of oxygen-irrelevant toxic free radicals, which exhibits great potential for clinical translations in hypoxic tumor therapy.