{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T12:11:46Z","timestamp":1791288706353,"version":"4.3.0"},"reference-count":35,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2018,5,20]],"date-time":"2018-05-20T00:00:00Z","timestamp":1526774400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Cyclodextrins (CDs) are cyclic oligosaccharides; the most common CDs contain six, seven, or eight glucose units called \u03b1-CDs, \u03b2-CDs, and \u03b3-CDs, respectively. The use of CDs in biomedical research is increasing due to their ability to interact with membrane lipids as well as a wide variety of poorly water-soluble molecules. We assessed the impact of CD cavity size, occupancy, and substitutions on cytotoxicity and cholesterol homeostasis. The potency of CD-mediated cytotoxicity was in the order of \u03b2-CDs, \u03b1-CDs, and \u03b3-CDs. Substitutions with hydroxypropyl or carboxymethyl group attenuated cytotoxicity compared with the native CDs, whereas CDs substituted with methyl groups exhibited cytotoxicity that was similar to that of the native CDs. The lipid components in blood exerted remarkable hemolysis-alleviating effects in methyl-\u03b2-CD-induced hemolysis. Occupancy of the CD cavity with cholesterol or a structurally related lipid molecule abrogated the cytotoxic capacity of the CDs. Interestingly, hydroxypropyl-\u03b3-CD (HP\u03b3CD) was able to reduce intracellular cholesterol accumulation in Niemann\u2013Pick disease type C (NPC) patient-derived fibroblasts as efficiently as HP\u03b2CD. Proteomic study indicated that HP\u03b2CD and HP\u03b3CD treatments altered the expression pattern of cellular proteins, suggesting that some of the CD-induced cellular proteins may play an important function in modulating intracellular cholesterol homeostasis.<\/jats:p>","DOI":"10.3390\/molecules23051228","type":"journal-article","created":{"date-parts":[[2018,5,21]],"date-time":"2018-05-21T04:07:30Z","timestamp":1526875650000},"page":"1228","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":127,"title":["Cyclodextrins: Assessing the Impact of Cavity Size, Occupancy, and Substitutions on Cytotoxicity and Cholesterol Homeostasis"],"prefix":"10.3390","volume":"23","author":[{"given":"Lajos","family":"Szente","sequence":"first","affiliation":[{"name":"Cyclolab Cyclodextrin Research and Development Laboratory Ltd., H-1097 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9172-1916","authenticated-orcid":false,"given":"Ashutosh","family":"Singhal","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Physiology, Meharry Medical College, Nashville, TN 37208, USA"},{"name":"Center for AIDS Health Disparities Research, Meharry Medical College, Nashville, TN 37208, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1722-708X","authenticated-orcid":false,"given":"Andras","family":"Domokos","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of California-Davis, Davis, CA 95616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byeongwoon","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Physiology, Meharry Medical College, Nashville, TN 37208, USA"},{"name":"Center for AIDS Health Disparities Research, Meharry Medical College, Nashville, TN 37208, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,5,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1038\/nrd1576","article-title":"Cyclodextrin-based pharmaceutics: Past, present and future","volume":"3","author":"Davis","year":"2004","journal-title":"Nat. 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