DNA Damage-Sensitized metal phenolic nanosynergists potentiate Low-Power phototherapy for osteosarcoma therapy

Non-invasive and efficient photodynamic therapy (PDT) holds great promise to circumvent resistance to traditional osteosarcoma (OS) treatments. Nevertheless, high-power PDT applied in OS often induces photothermogenesis, resulting in normal cells rupture, sustained inflammation and irreversible vascular damage. Despite its relative safety, low-power PDT fails to induce severe DNA damage for insufficient reactive oxygen species (ROS) production. Herein, a non-ROS-dependent DNA damage-sensitizing strategy is introduced in low-power PDT to amplify the therapeutic efficiency of OS, where higher apoptosis is achieved with low laser power. Inspired by the outstanding DNA damage performance of tannic acid (TA), TA-based metal phenolic networks (MPNs) are engineered to encapsulate hydrophobic photosensitizer (purpurin 18) to act as DNA damage-sensitized nanosynergists (TCP NPs). Specially, under low-power laser irradiation, the TCP NPs can boost ROS instantly to trigger mitochondrial dysfunction simultaneously with upregulation of DNA damage levels triggered by TA to reinforce PDT sensitization, evoking potent antitumor effects. In addition, TCP NPs exhibit long-term retention in tumor, greatly benefiting sustained antitumor performances. Overall, this study sheds new light on promoting the sensitivity of low-power PDT by strengthening DNA damage levels and will benefits advanced OS therapy.