Copper sulfide nanoparticles as a photothermal switch for TRPV1 signaling to attenuate atherosclerosis

Atherosclerosis is characterized by the accumulation of lipids within the arterial wall. Although activation of TRPV1 cation channels by capsaicin may reduce lipid storage and the formation of atherosclerotic lesions, a clinical use for capsaicin has been limited by its chronic toxicity. Here we show that coupling of copper sulfide (CuS) nanoparticles to antibodies targeting TRPV1 act as a photothermal switch for TRPV1 signaling in vascular smooth muscle cells (VSMCs) using near-infrared light. Upon irradiation, local increases of temperature open thermo-sensitive TRPV1 channels and cause Ca²⁺ influx. The increase in intracellular Ca²⁺ activates autophagy and impedes foam cell formation in VSMCs treated with oxidized low-density lipoprotein. In vivo, CuS-TRPV1 allows photoacoustic imaging of the cardiac vasculature and reduces lipid storage and plaque formation in ApoE^-/^- mice fed a high-fat diet, with no obvious long-term toxicity. Together, this suggests CuS-TRPV1 may represent a therapeutic tool to locally and temporally attenuate atherosclerosis.