Overcoming Radioresistance in Tumor Therapy by Alleviating Hypoxia and Using HIF-1 Inhibitor.

Radiotherapy has been extensively used to treat cancer patients because it can effectively damage most solid tumors without penetration limits. A hypoxic microenvironment in solid tumors leads to severe radioresistance and expression of hypoxic inducible factor-1 (HIF-1), both which result in poor efficacy of radiotherapy alone. Herein, we report the excellent efficacy of radiotherapy achieved by using a new type of yolk-shell Cu2-xSe@PtSe (CSP) nanosensitizer functionalized with the HIF-1α inhibitor acriflavine (ACF). We prepare the CSP nanosensitizer through the interfacial redox reactions between chloroplatinic acid and Cu2-xSe nanoparticles (CS), and then functionalize the nanosensitizer with ACF through their electrostatic interactions. We show that the synthesized CSP nanosensitizer can arrest the cell cycle (i.e. at the gap 2/mitosis (G2/M) phases) of tumor cells to enhance their sensitivity to X-rays, and decompose endogenous H2O2 into O2 to reduce hypoxia and increase the production of reactive o...