{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:58:23Z","timestamp":1791824303421,"version":"4.3.4"},"reference-count":62,"publisher":"American Society for Clinical Investigation","issue":"22","license":[{"start":{"date-parts":[[2024,11,15]],"date-time":"2024-11-15T00:00:00Z","timestamp":1731628800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81830080"],"award-info":[{"award-number":["81830080"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82121002"],"award-info":[{"award-number":["82121002"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,11,15]]},"abstract":"<jats:p>Liposomal drug delivery systems have revolutionized traditional cytotoxic drugs. However, the relative instability and toxicity of the existing liposomal drug delivery systems compromised their efficacy. Herein, we present Rg3-lipo, an innovative drug delivery system using a glycosyl moiety\u2013enriched ginsenoside (Rg3). This system is distinguished by its glycosyl moieties exposed on the liposomal surface. These moieties imitate human cell membranes to stabilize and evade phagocytic clearance. The Rg3-lipo system loaded with paclitaxel (PTX-Rg3-lipo) demonstrated favorable bioavailability and safety in Sprague-Dawley rats, beagle dogs, and cynomolgus monkeys. With its glycosyl moieties recognizing tumor cells via the glucose transporter Glut1, PTX-Rg3-lipo inhibited gastric, breast, and esophageal cancers in human cancer cell lines, tumor-bearing mice, and patient-derived xenograft models. These glycosyl moieties selectively targeted myeloid-derived suppressor cells (MDSCs) through the glucose transporter Glut3 to attenuate their immunosuppressive effect. The mechanism study revealed that Rg3-lipo suppressed glycolysis and downregulated the transcription factors c-Maf and Mafb overcoming the MDSC-mediated immunosuppressive microenvironment and enhancing PTX-Rg3-lipo\u2019s antitumor effect. Taken together, we supply substantial evidence for its advantageous bioavailability and safety in multiple animal models, including nonhuman primates, and Rg3-lipo\u2019s dual targeting of cancer cells and MDSCs. Further investigation regarding Rg3-lipo\u2019s druggability will be conducted in clinical trials.<\/jats:p>","DOI":"10.1172\/jci178617","type":"journal-article","created":{"date-parts":[[2024,11,14]],"date-time":"2024-11-14T14:00:36Z","timestamp":1731592836000},"source":"Crossref","is-referenced-by-count":28,"title":["Rg3-lipo biomimetic delivery of paclitaxel enhances targeting of tumors and myeloid-derived suppressor cells"],"prefix":"10.1172","volume":"134","author":[{"given":"Yuru","family":"Shen","sequence":"first","affiliation":[{"name":"Department of Digestive Diseases and National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Digestive Diseases and National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China."},{"name":"Biotherapy Research Center, Fudan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanwei","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Digestive Diseases and National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Wang","sequence":"additional","affiliation":[{"name":"Xiamen Ginposome Pharmaceutical Co. Ltd., Xiamen, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Digestive Diseases and National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Digestive Diseases and National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuanxuan","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Digestive Diseases and National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaocong","family":"Mo","sequence":"additional","affiliation":[{"name":"Department of Digestive Diseases and National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Digestive Diseases and National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoshu","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Digestive Diseases and National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huaxing","family":"Zhan","sequence":"additional","affiliation":[{"name":"Xiamen Ginposome Pharmaceutical Co. Ltd., Xiamen, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3834-0188","authenticated-orcid":true,"given":"Feifei","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Digestive Diseases and National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Digestive Diseases and National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2024,11,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drup.2021.100796"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2020.07.002"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2023.114901"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.cis.2023.102930"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2004.01.011"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2020.07.016"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2021.113851"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2018.06.005"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2022.09.031"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1080\/14686996.2019.1627174"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2015.10.022"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2017.05.016"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1080\/17425255.2021.1943358"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-022-00546-2"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2018.10.008"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-020-00490-y"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2021.04.004"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-017-0022-x"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-21-0764"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1172\/JCI170762"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2017.2857"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2020.12.036"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abj1262"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-020-00390-6"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1007\/s40820-020-00472-8"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.7150\/thno.34953"},{"issue":"4","key":"B27","first-page":"495","article-title":"Fifty years chlorpromazine: a historical perspective","volume":"3","author":"Ban","year":"2007","journal-title":"Neuropsychiatr Dis Treat"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2703"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.14570"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2018.04.022"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03442-1"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2020.05.004"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-018-2177-1"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109955"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20182005"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2017.07.020"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0145342"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2017.08.016"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx1013"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1126\/science.1176056"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-023-01468-3"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.04.057"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2022.09.007"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24032643"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.2147\/IJN.S228715"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.3881\/j.issn.1000-503X.2014.03.014"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1002\/btm2.10284"},{"issue":"7","key":"B48","first-page":"517","article-title":"[A randomized controlled trial of two chemotherapy regimens (paclitaxel liposome combined with platinum and paclitaxel combined with platinum) in concurrent chemoradiotherapy for cervical carcinoma]","volume":"33","author":"Zeng","year":"2011","journal-title":"Zhonghua Zhong Liu Za Zhi"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-16-0297"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-021-00670-9"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-022-01335-y"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-022-01657-y"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-30326-3"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2022.02.015"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2023.07.001"},{"key":"B56","unstructured":"Wang D, et al. The method of preparation and the application of the ginsenoside paclitaxel liposome: CN114432245B. https:\/\/patents.google.com\/patent\/CN114432245B\/en Published May 6, 2022. Granted October 3, 2023. Accessed October 16, 2024"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpb.2018.04.003"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2021.03.055"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1038\/s43018-021-00245-1"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-13-2347"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2010.05.010"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.113661"}],"container-title":["Journal of Clinical Investigation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.jci.org\/articles\/view\/178617\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T23:00:05Z","timestamp":1779231605000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jci.org\/articles\/view\/178617"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,15]]},"references-count":62,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2024,11,15]]},"published-print":{"date-parts":[[2024,11,15]]}},"alternative-id":["10.1172\/JCI178617"],"URL":"https:\/\/doi.org\/10.1172\/jci178617","relation":{},"ISSN":["1558-8238"],"issn-type":[{"value":"1558-8238","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,15]]},"article-number":"e178617"}}