A\nNano-Aggregatable Acedan Derivative for Clathrin-Mediated\nCellular Uptake and Two-Photon Imaging of Diabetes-Associated Lipid\nDroplets

Lipid\ndroplets (LDs), the essential cytosolic fat storage organelles,\nhave emerged as pivotal regulators of cellular metabolism and are\nimplicated in various diseases. The noninvasive monitoring of LDs\nnecessitates fluorescent probes with precise organelle selectivity\nand biocompatibility. Addressing this need, we have engineered a probe\nby strategically modifying the structure of a conventional two-photon-absorbing\ndipolar dye, acedan. This innovative approach induces nanoaggregate\nformation in aqueous environments, leading to aggregation-induced\nfluorescence quenching. Upon cellular uptake via clathrin-mediated\nendocytosis, the probe selectively illuminates within LDs through\na disassembly process, effectively distinguishing LDs from the cytosol\nwith exceptional specificity. This breakthrough enables the high-fidelity\nimaging of LDs in both cellular and tissue environments. In a pioneering\ninvestigation, we probed LDs in a diabetes model induced by streptozotocin,\nunveiling significantly heightened LD accumulation in cardiac tissues\ncompared to other organs, as evidenced by TP imaging. Furthermore,\nour exploration of a lipopolysaccharide-mediated cardiomyopathy model\nrevealed an LD accumulation during heart injury. Thus, our developed\nprobe holds immense potential for elucidating LD-associated diseases\nand advancing related research endeavors.