Single-walled carbon nanotubes hitchhike on Ly-6Chi monocytes for photoacoustic image-guided photothermal shock therapy of metabolic inflammation

Abstract

Metabolic inflammation (metaflammation) may occur throughout the body and evolve into various metabolic syndromes, so developing a universal approach for diagnosing and treating metaflammation is meaningful. Here, we developed a single-walled carbon nanotube (SWNT)-based photothermal shock therapy (PTST) for photoacoustic image-guided therapy of metaflammation. Mechanistically, SWNTs are specifically taken up by Ly-6C^hi monocytes in peripheral blood and then rerouted to inflamed tissues via Ly-6C^hi monocyte hitchhiking. Due to the accumulation of SWNTs, inflamed tissues can be distinguished by photoacoustic imaging. For treating metaflammation, inflamed tissue gated by photoacoustic imaging is irradiated with near-infrared light and heated to heat shock temperature (around 42 °C). At this temperature, lesional macrophages upregulate the expression of HSP70, which blocks the activation of inflammatory pathways and protects cells from metabolic and inflammatory stress. We successfully identified the lesional liver and aorta and implemented PTST in type 2 diabetes and atherosclerosis model mice. Compared with traditional photothermal therapy (PTT), PTST controls the temperature in a safer and narrower range, implying the prospect of precise temperature control in disease treatment.