Biodegradable PLGA Particles with Confined Water for Safe Photothermal Biomodulation

Photothermal biomodulation is an emerging technique that leverages the deep optical penetration of near-infrared light in biological tissues, enabling a range of diagnostic and therapeutic applications. Given that photothermal agents are used within the body, ensuring long-term safety is essential, necessitating the development of safer, biodegradable agents. In this work, we developed biodegradable photothermal particles based on the FDA-approved polylactic-<i>co</i>-glycolic acid (PLGA) polymer and confined water. We hypothesize that confined water acts as a photothermal transducer due to its lower heat capacity compared to surrounding bulk water, while the polymer layer provides thermal insulation, effectively retaining the generated heat within the particles and creating a thermal gradient in their immediate vicinity. Fluorescent thermometry and IR camera results demonstrate the strong photothermal performance of the developed particles, enabling localized heating instead of global heating in surrounding environments. Additionally, we confirm the presence of confined water within the particles through Fourier transform infrared (FTIR) and X-ray diffraction (XRD) results. Further in vitro validation using lysozyme enzyme activity tests and cell viability experiments with EO771 cancer cells expressing LanYFP fluorescent protein confirmed the biocompatibility and efficacy of the developed particles. These particles successfully induced localized heating in the cellular environment without compromising cell viability, making them highly promising for safe biomedical applications in photothermal therapy and biomodulation.