LAUSR

Although various types of radiosensitizers based on nanoparticles are explored to enhance radiotherapy via different mechanisms, nanoscale radiosensitizers with full biodegradability, sensitive responsiveness to the tumor microenvironment, as well as the ability to greatly amplify radiation-induced tumor destruction are still demanded. Herein, this study designs nanoscale coordination polymers (NCPs) based on acidic sensitive linker and high Z number element hafnium (Hf) ions. Chloro(triphenylphosphine)gold(I) (TPPGC), a chemotherapeutic drug, is successfully loaded into those NCPs after they are coated with polyethylene glycol (PEG). Owing to the acid-triggered cleavage of the organic linker, such formed NCP-PEG/TPPGC nanoparticles would be dissociated under reduced pH within the tumor, leading to the release of TPPGC to induce mitochondrial damage and arrest the cell cycle of tumor cells into the radiosensitive phase (G1). Meanwhile, Hf ions are able to act as radiosensitizers by absorbing X-ray and depositing radiation energy within tumors. With efficient tumor accumulation after intravenous injection, NCP-PEG/TPPGC offers remarkable synergistic therapeutic outcome in chemoradiotherapy without appreciable toxic side effect. This work thus presents a biodegradable nano-radiosensitizer with in vivo tumor-specific decomposition/drug release profiles and great efficacy in chemoradiotherapy of cancer.