In Vivo Three‐Photon Imaging of Lipids using Ultrabright Fluorogens with Aggregation‐Induced Emission

Abstract Fluorescent probes capable of in vivo lipids labeling are highly desirable for studying lipid‐accumulation‐related metabolic diseases, such as nonalcoholic fatty liver disease, type‐2 diabetes, and atherosclerosis. However, most of the current lipid‐specific fluorophores cannot be used for in vivo labeling due to their strong hydrophobicity. Herein, organic dots from bright luminogens with aggregation‐induced emission (AIEgen) are developed for in vivo labeling and three‐photon fluorescence imaging of lipid‐rich tissues, such as fatty liver, atherosclerotic plaques in brain vasculatures, and carotid arteries. The organic dots show excellent stability in an aqueous medium with high targeting specificity to lipids and strong three‐photon fluorescence in the far‐red/near‐infrared (NIR) region under NIR‐II laser excitation, which enables efficient in vivo labeling and imaging of lipids in deep tissues. The study will inspire the development of lipid‐targeting fluorophores for in vivo applications.