Thermal responsive nanobombs generating reactive oxygen species for synergistic anticancer therapy

The nano-based therapeutics to induce cellular oxidative damage is considered promising in cancer treatment. Photodynamic therapy (PDT) is a primary antitumor oxidative damage treatment method. However, the hypoxic environment of tumor tissues and the short lifetime of singlet oxygen significantly hampers PDT efficacy. Fortunately, nitric oxide (NO), as a form of gas therapy, can generate more toxic oxidative peroxynitrite ions (ONOO⁻) with hydrogen peroxide (H₂O₂), which significantly enhance the efficacy of PDT. In this context, we fabricated a thermally controlled reactive oxygen nanobombs CaO₂@LA-ICG@TD (CAI@TD), which can release many reactive oxygen species (ROS) to enhance the synergistic anticancer efficiency under a. The cellular studies revealed that CAI@TD could produce oxygen and H₂O₂ to heighten the efficacy of PDT and NO and induce necrotic-apoptosis of MDA-MB-231 cells by mitochondria damage, lipid peroxidation, and DNA fragments. Moreover, CAI@TD with 808 nm laser irradiation achieved a significant inhibition on the xenograft tumor growth. This work provides an efficient strategy to produce a high amount of ROS for synergistic anticancer therapy, offering a ray of hope in the fight against cancer.