Photothermal Oxygen-Releasing IR780/CaO₂ Nanoplatform for Enhanced and On-Demand Photodynamic Therapy

Tumor hypoxia is a major challenge in photodynamic therapy (PDT) of cancer because PDT efficacy strongly depends on oxygen availability. Here, we report the first fabrication of an on-demand oxygen-releasing solid lipid nanoplatform comprising IR780 and CaO 2 nanoparticles (IRCa@SLN) with an average size of 94.5 ± 2.1 nm to enhance PDT efficacy. Low-power photothermal activation of IRCa@SLN by a 200 mW, 808 nm laser enabled on-demand CaO 2 release. The laser-activated CaO 2 locally generated oxygen and reactive oxygen species (ROS) through interaction with water, enhancing PDT efficacy, as confirmed by a photonic-based dissolved oxygen (DO) sensor based on time-resolved phosphorescence spectroscopy. Enhanced PDT was demonstrated using MDA-MB-231 cells, where IRCa@SLN (0.065 μg/mL IR780) exhibited 73.5 ± 9.8% reduction in cell viability and enhanced intracellular ROS generation compared to the control after 5 min of treatment with an 808 nm NIR laser at 40 mW/mm 2 . Without laser irradiation, there was no significant change in the intracellular ROS level and cell viability at this nanoparticle concentration. In contrast, IR780@SLN (nanoplatform without CaO 2 ) showed no cell toxicity with or without laser irradiation at an equivalent IR780 concentration. These findings highlight the enhanced PDT effect due to CaO 2 nanoparticles and light responsiveness of IRCa@SLN.