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 CaO2 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 CaO2 release. The laser-activated CaO2 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/mm2. 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 CaO2) showed no cell toxicity with or without laser irradiation at an equivalent IR780 concentration. These findings highlight the enhanced PDT effect due to CaO2 nanoparticles and light responsiveness of IRCa@SLN.