Biomimetic Copper Sulfide for Chemo-Radiotherapy: Enhanced Uptake and Reduced Efflux of Nanoparticles for Tumor Cells under Ionizing Radiation

Combined chemo-radiotherapy is one of most widely applied treatments for clinical cancer therapy. Herein, it is found in this carefully designed study that ionizing radiation (e.g., X-ray) can significantly increase the cell uptake of many different types of nanoparticles, and meanwhile obviously reduce their efflux. Such a phenomenon, which is not observed for small molecule drug such as doxorubicin (DOX), may be attributed to the X-ray-induced cell cycle change and upregulation of Caveolin-1, a key protein in the caveolin-dependent endocytosis pathway. Biomimetic copper sulfide nanoparticles, which are synthesized using melanin as the template and functionalized with polyethylene glycol (PEG), are then chosen as a platform for the combined chemo-radiotherapy. Such CuS@Melanin-PEG nanoparticles, while being able to load chemotherapeutics (e.g., DOX), can also act as a radiosensitizer to promote X-ray induced cell apoptosis. In addition, although the overall tumor accumulation of CuS@Melanin-PEG/DOX post intravenous injection is not significantly changed for tumors exposed to X-ray, X-ray radiation can result in obviously increased tumor cell uptake of drug-loaded nanoparticles, subsequently leading to excellent synergistic antitumor therapeutic effect. A nanoplatform is developed with great performance in chemo-radiotherapy, as well as uncovers a general synergistic mechanism particularly suitable for nanoparticle-based chemo-radiotherapy.