Photothermal Oxygen-Releasing\nIR780/CaO<sub>2</sub> Nanoplatform for Enhanced and On-Demand Photodynamic\nTherapy

Tumor hypoxia is a major challenge in photodynamic therapy\n(PDT)\nof cancer because PDT efficacy strongly depends on oxygen availability.\nHere, we report the first fabrication of an on-demand oxygen-releasing\nsolid lipid nanoplatform comprising IR780 and CaO<sub>2</sub> nanoparticles\n(IRCa@SLN) with an average size of 94.5 ± 2.1 nm to enhance PDT\nefficacy. Low-power photothermal activation of IRCa@SLN by a 200 mW,\n808 nm laser enabled on-demand CaO<sub>2</sub> release. The laser-activated\nCaO<sub>2</sub> locally generated oxygen and reactive oxygen species\n(ROS) through interaction with water, enhancing PDT efficacy, as confirmed\nby a photonic-based dissolved oxygen (DO) sensor based on time-resolved\nphosphorescence spectroscopy. Enhanced PDT was demonstrated using\nMDA-MB-231 cells, where IRCa@SLN (0.065 μg/mL IR780) exhibited\n73.5 ± 9.8% reduction in cell viability and enhanced intracellular\nROS generation compared to the control after 5 min of treatment with\nan 808 nm NIR laser at 40 mW/mm<sup>2</sup>. Without laser irradiation,\nthere was no significant change in the intracellular ROS level and\ncell viability at this nanoparticle concentration. In contrast, IR780@SLN\n(nanoplatform without CaO<sub>2</sub>) showed no cell toxicity with\nor without laser irradiation at an equivalent IR780 concentration.\nThese findings highlight the enhanced PDT effect due to CaO<sub>2</sub> nanoparticles and light responsiveness of IRCa@SLN.