Laser-responsive chitosan-coated solid lipid nanoparticles co-encapsulating CaO₂ nanoparticles and IR780 for on-demand and enhanced photodynamic therapy of cancers

The photodynamic therapy (PDT) efficacy is limited by tumor hypoxia and inefficient intracellular accumulation of photosensitizers (PSs). This study reports chitosan-coated solid lipid nanoparticles (SLNs) co-encapsulating the near-infrared photosensitizer IR780 and oxygen-generating CaO₂ nanoparticles (NPs) for on-demand and enhanced PDT. Under 808 nm laser irradiation, the resulting IRCa@SLN-CH nanoplatform undergoes phase change due to IR780 photothermal effects, triggering the release of IR780 and CaO₂. The released CaO₂ subsequently hydrolyzes to generate oxygen in situ, boosting singlet oxygen production by IR780. Successful chitosan coating was confirmed by FTIR spectroscopy and a zeta potential shift from -36.2 ± 3.6 mV (uncoated IRCa@SLN) to + 35.3 ± 6.6 mV (IRCa@SLN-CH). IRCa@SLN-CH exhibited an average particle size of 51.5 ± 19.3 nm by TEM and 77.6 ± 7.0 nm by DLS, with IR780 and CaO₂ loadings of 4.23 ± 0.23% and 65 ± 7%, respectively. Dissolved oxygen (DO) and ROS measurements showed that chitosan coating improved payload protection, resulting in a more controlled, on-off activation profile in response to laser irradiation. In vitro tests using MDA-MB-231 breast cancer cells demonstrated that chitosan coating enhanced cellular uptake, increased on-demand intracellular ROS generation, and improved laser-responsive cytotoxicity, while maintaining low ROS generation and toxicity before laser activation. Cell viability remained high before irradiation (99 ± 1%) but reduced to 51 ± 3% following laser exposure. Overall, the IRCa@SLN-CH nanoplatform shows potential for on-demand and enhanced PDT.