Proof of concept for dual anticancer effects by a novel nanomaterial-mediated cancer cell killing and nano-radiosensitization

Nano‐radiosensitization is an emerging concept for cancer therapy and the underlying rationale embroils enhancement of radiosensitization by nanomaterials. Here we describe a new concept of the irradiation-triggered switching of a biologically inert nano-prodrug to releasing an anticancer gas that executes cancer cells killing and improves radiosensitization by improving the tumor hypoxic microenvironment. This novel strategy employed chemical coordination between radiosensitive gold-coated polyethylene glycol (PEG) nanoparticles and nanoclusters (AuNCs-PEG) and sodium nitroprusside (SNP) coated by platelet membranes (PM) to generate AuNCs-PEG-SNP-PM (APS), which upon irradiation released a high content of anticancer nitric oxide (NO) through a reaction of SNP and L-glutathione (GSH). NO inhibited cell respiration and O2 consumption through the downregulation of hypoxia inducible factor-1α (HIF-1α). Consequently, O2 accumulation improved therapeutic outcomes by generating ROS in the tumor microenvironment. In preclinical cancer models, we showed that this approach nearly completely eradicated tumors without producing any notable adverse effects. Our therapeutic strategy may provide a new paradigm for effective treatment of various types of cancers.