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This study aimed to develop a liposomal strategy based on its proven clinical biosafety, well\u2010known membrane trafficking behavior, and potential to act as membrane cholesterol\u2010specific detergents. Addition of cholesterol or detergent (Triton X\u2010100) into liposomal membranes laundered cell membrane cholesterol equivalently, thereby improving cellular uptake of drug molecules. However, only the detergent\u2010containing liposomes caused cytotoxicity as liposomal concentrations increased, justifying the use of cholesterol (+)\u2010liposomes. The hypoxic status of patient HCCs elevated lipidation, which was laundered by liposomal treatment. Consequent drug uptake and therapeutic effects were improved in cancer cells, 3D spheroids, and patient\u2010derived HCC tissues using perfusion\u2010based 3D chip systems. Uptake of hydrophobic drug was also improved to a greater extent compared to hydrophilic ones across these models. In mouse fatty livers, IV injection of cholesterol (+)\u2010liposomes alone decreased hepatic lipidation, inflammation, and fibrosis. When the plasma membrane forms endosomes by encapsulating the liposomes after uptake, membrane cholesterol is transferred from the endosomes to the liposomes and subsequently metabolized in the endoplasmic reticulum (ER). This mechanism was validated using endosome\u2010mimetic nanovesicles and biochemical ER regulators. The results indicate the promising potential of cholesterol (+)\u2010liposomes to improve HCC therapy.<\/jats:p>","DOI":"10.1002\/advs.76144","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T13:05:12Z","timestamp":1781701512000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cholesterol Laundry of Cell Membrane and Fatty Liver by Detergent Liposomes to Improve Anti\u2010Cancer Drug Responsiveness of Patient Liver Tissues"],"prefix":"10.1002","volume":"13","author":[{"given":"Chansik","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Medical Engineering Graduate School of Medical Science Brain Korea 21 Project Yonsei University College of Medicine  Seoul South Korea"},{"name":"Department of Medical Engineering Yonsei University College of Medicine  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joo 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