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In this study, we report BTDO\u2010MEA, a fluorescent probe with a donor\u2013acceptor structure for high\u2010resolution imaging of intracellular LD polarity. BTDO\u2010MEA shows excellent lipophilicity, a large Stokes shift, and a large linear fluorescence lifetime response to environmental polarity. We further demonstrated BTDO\u2010MEA as a FLIM probe to visualize polarity changes of LDs in living cells. The probe enables discrimination the polarity differences between the core and the periphery of intracellular LDs. Upon oleic acid treatment, the overall lifetime of the LDs increased from 1.5 to 3\u00a0ns, indicating a significant polarity decrease in the periphery the LDs during the acute lipid accumulation process. These results demonstrate BTDO\u2010MEA could be used as a useful imaging tool for monitoring lipid accumulation and studying lipid\u2010associated metabolic disorders.<\/jats:p>","DOI":"10.1002\/chem.71638","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T04:30:02Z","timestamp":1787805002000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Polarity\u2010Sensitive FLIM Probe With Large Lifetime Dynamic Range for Visualizing Intracellular Lipid Droplets"],"prefix":"10.1002","author":[{"given":"Sixue","family":"Tang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Quantum Functional Materials School of Physical Science and Technology ShanghaiTech University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongjuan","family":"Si","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory of Smart Drug Delivery MOE 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