{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T16:28:30Z","timestamp":1790872110785,"version":"4.1.0"},"reference-count":58,"publisher":"Wiley","issue":"34","license":[{"start":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T00:00:00Z","timestamp":1750723200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82204308"],"award-info":[{"award-number":["82204308"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Small"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Anti\u2010polyethylene glycol (PEG) antibodies exist in many individuals and may lead to accelerated blood clearance (ABC) of PEGylated liposomes. However, the prevalence of the ABC phenomenon in individuals has remained unclear due to the absence of an effective prediction method. In this study, a drug\u2010release reporter liposome is developed by encapsulating rapidly activated 7\u2010ethyl\u201010\u2010hydroxycamptothecin (SN38)\u2010glutathione (GSH) within the liposomes, enabling to accurately assess drug release in plasma based on the SN38\/(SN38+SN38\u2010GSH) ratio. Utilizing this liposome, it is found that plasma\u2010induced accelerated drug release (ADR) is strongly correlated with the ABC phenomenon of PEGylated liposomes in rats. Importantly, ADR proved to be a more accurate predictor of the ABC phenomenon than the presence of anti\u2010PEG antibodies. ADR analysis of 1764 human samples indicated that only a low incidence (0.28%) of individuals undergoes the ABC phenomenon at a clinically relevant dose of commercial PEGylated liposomes of doxorubicin (DOXIL). A relatively high ratio (5%) of individuals may encounter the ABC phenomenon at a low dose (\u22481\/10 of the DOXIL dose). In summary, ADR is proposed as a new parameter to predict the ABC phenomenon of PEGylated liposomes and conclude that the pre\u2010existing anti\u2010PEG antibodies are unlikely to predict reliably the ABC phenomenon of DOXIL in humans.<\/jats:p>","DOI":"10.1002\/smll.202500526","type":"journal-article","created":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T06:20:32Z","timestamp":1750746032000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Revealing the Incidence of the Accelerated Blood Clearance Phenomenon of PEGylated Liposomes in Individuals Using a Drug\u2010Release Reporter Liposome"],"prefix":"10.1002","volume":"21","author":[{"given":"Yaxin","family":"Zheng","sequence":"first","affiliation":[{"name":"School of Pharmacy Key Laboratory of Sichuan Province for Specific Structure of Small Molecule Drugs Chengdu Medical College  Chengdu 610500 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine the Second Affiliated Hospital of Chengdu Medical College Nuclear Industry 416 Hospital  Chengdu 610057 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hailong","family":"Ma","sequence":"additional","affiliation":[{"name":"School of Pharmacy Key Laboratory of Sichuan Province for Specific Structure of Small Molecule Drugs Chengdu Medical College  Chengdu 610500 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongling","family":"Xu","sequence":"additional","affiliation":[{"name":"School of Pharmacy Key Laboratory of Sichuan Province for Specific Structure of Small Molecule Drugs Chengdu Medical College  Chengdu 610500 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Can","family":"Yin","sequence":"additional","affiliation":[{"name":"School of Pharmacy Key Laboratory of Sichuan Province for Specific Structure of Small Molecule Drugs Chengdu Medical College  Chengdu 610500 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yihong","family":"Su","sequence":"additional","affiliation":[{"name":"School of Pharmacy Key Laboratory of Sichuan Province for Specific Structure of Small Molecule Drugs Chengdu Medical College  Chengdu 610500 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuyang","family":"Li","sequence":"additional","affiliation":[{"name":"School of Pharmacy Key Laboratory of Sichuan Province for Specific Structure of Small Molecule Drugs Chengdu Medical College  Chengdu 610500 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6924-1297","authenticated-orcid":false,"given":"Yang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics College of Pharmacy Chongqing Medical University  Chongqing 400016 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,6,24]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3565(24)35391-1"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-3659(02)00462-5"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2013.07.026"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2006.01.005"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2006.08.001"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(01)00129-7"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2005.04.003"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(20000901)89:5<1037::AID-CNCR13>3.0.CO;2-Z"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2006.08.017"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1211\/jpp.60.12.0011"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-011-1664-2"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2020.07.024"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.1c05922"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.molpharmaceut.3c00774"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2023.01.012"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/wnan.1339"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nantod.2024.102163"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.22164"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2023.09.003"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2022.121539"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2022.121415"},{"key":"e_1_2_9_22_1","volume":"13","author":"Berger M.","year":"2024","journal-title":"Adv. Healthcare Mater."},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.3c02762"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2025.113762"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2021.08.051"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2019.06.007"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2019.08.017"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2023.08.052"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.molpharmaceut.4c00278"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2011.06.017"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2023.115044"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2021.11.042"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.9b07218"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1039\/D2MH00380E"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.4c05409"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1039\/D0NR04100A"},{"key":"e_1_2_9_37_1","first-page":"83","volume":"150","author":"Harris C. L.","year":"2000","journal-title":"Methods Mol Biol"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200342050-00002"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.6b03109"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.2217\/17435889.1.3.297"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2006.01.005"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.b14-00653"},{"key":"e_1_2_9_43_1","first-page":"1257","volume":"8","author":"Yang Q.","year":"2013","journal-title":"Int J Nanomedicine"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2015.06.005"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2012.03.020"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.2c04543"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.4c11652"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-022-00825-x"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1080\/14686996.2019.1627174"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.4c13214"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1039\/D2TB00672C"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.0c06679"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.4c09919"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.molpharmaceut.5b00144"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2012.11.016"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2008.05.010"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aba6322"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/s44222-023-00138-1"}],"container-title":["Small"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/smll.202500526","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T13:57:19Z","timestamp":1756389439000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/smll.202500526"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,24]]},"references-count":58,"journal-issue":{"issue":"34","published-print":{"date-parts":[[2025,8]]}},"alternative-id":["10.1002\/smll.202500526"],"URL":"https:\/\/doi.org\/10.1002\/smll.202500526","archive":["Portico"],"relation":{},"ISSN":["1613-6810","1613-6829"],"issn-type":[{"value":"1613-6810","type":"print"},{"value":"1613-6829","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,24]]},"assertion":[{"value":"2025-01-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-24","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2500526"}}