Harnessing Dye-induced Photothermal Confinement in Lipid Membranes: A Path to NIR-modulated Artificial Synaptic Vesicles

Optical heating coupled with near-infrared (NIR) light and photothermal materials enables thermal confinement within biospecimens, minimizing undesirable thermal damage. Here, we demonstrated that photothermally heating lipid bilayers embedded with a unique phthalocyanine dye (VPc) efficiently perturbs the bilayers, resulting in increased permeability. Notably, microscopic studies revealed that the mechanism causing changes in membrane permeability may not follow the conventional temperature-sensitive liposome model. Furthermore, the heat generated by NIR laser illumination rarely diffused into the surrounding environment, and the dye was located within the bilayers at the molecular level, where it effectively transferred heat to the lipid bilayer. We prepared VPc-embedded liposomes encapsulating acetylcholine (ACh) and demonstrated the NIR laser-triggered release of ACh, creating a concentration jump across a few cells or within a limited single cell region. This method induced Ca ²⁺ flux through ACh receptor stimulation in thermally delicate biospecimens such as C2C12 myotubes and the Drosophila brain.