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However, the lack of biocompatible contrast agents with bright NIR\u2010II emission has hampered the precise clinical application of deep tissue imaging. Here, a lipophilic enhancement strategy employing donor\u2010acceptor\u2010donor (D\u2010A\u2010D) molecules, introducing long alkoxy chains and quaternary ammonium salts for the development of highly bright water\u2010soluble NIR\u2010II fluorophores (BBTD\u20102C\u2010N), is described. Notably, liposome\u2010encapsulated BBTD\u20102C\u2010N nanoparticles (B\u20102C\u2010N\/DMPC) in aqueous solution exhibit a 1.8\u2010fold increase in NIR\u2010II fluorescence brightness compared to free BBTD\u20102C\u2010N in methanol. Avoidance of the aggregation\u2010caused quenching effect and enhanced NIR\u2010II fluorescence are attributed to significantly attenuated \u03c0\u2013\u03c0 stacking interactions and maintained monodisperses in the hydrophobic liposome shell. Moreover, BBTD\u20102C\u2010N demonstrates superior performance in visualizing lipid droplet\u2010rich HeLa cells in vitro, as well as precise monitoring of adipose tissue and fatty liver in vivo. This study reveals a new avenue for the development of bright NIR\u2010II fluorophores and precise in vivo imaging.<\/jats:p>","DOI":"10.1002\/smll.202406159","type":"journal-article","created":{"date-parts":[[2024,10,10]],"date-time":"2024-10-10T09:53:31Z","timestamp":1728554011000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Water\u2010Soluble Lipophilic Near\u2010Infrared Region II Fluorophores for High\u2010Brightness Lipid Layer and Lipid Droplets Imaging Applications"],"prefix":"10.1002","volume":"20","author":[{"given":"Sicheng","family":"Xu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Organic Electronics and Information Displays &amp; Jiangsu Key Laboratory for Biosensors Institute of Advanced Materials (IAM) Nanjing University of Posts &amp; Telecommunications  Nanjing 210023 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