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One Stone Four Birds:A Novel Liposomal Delivery System Multi-functionalized with Ginsenoside Rh2 for Tumor Targeting Therapy

查看全文 作　　者：Chao [1]Hong;Jianming [1,2]Liang;Jiaxuan [1]Xia;Ying [3]Zhu;Yizhen [1]Guo;Anni [1]Wang;Chunyi [4]Lu;Hongwei [1]Ren;Chen [1]Chen;Shiyi [1]Li;Dan [1,5]Wang;Huaxing [5]Zhan;Jianxin [1,6]Wang 高影响力作者 机构地区：[1]Department of Pharmaceutics,School of Pharmacy,Fudan University&Key Laboratory of Smart Drug Delivery,Ministry of Education,Shanghai 201203,People’s Republic of China;[2]Institute of Tropical Medicine,Guangzhou University of Chinese Medicine,Guangzhou 510006,People’s Republic of China;[3]Institute of Clinical Pharmacology,Guangzhou University of Chinese Medicine,Guangzhou 510006,People’s Republic of China;[4]School of Pharmacy,Shanghai Jiao Tong University,Shanghai 200240,People’s Republic of China;[5]Shanghai Ginposome Pharmatech Co.,Ltd,Shanghai 201600,People’s Republic of China;[6]Institute of Integrated Chinese and Western Medicine,Fudan University,Shanghai 200040,People’s Republic of China高影响力机构 出　　处：《Nano-Micro Letters》索引2020年第12卷第10期,共18页高影响力期刊 基　　金：supported by National Natural Science Foundation of China(Nos.81773911,81690263 and 81573616);the Development Project of Shanghai Peak Disciplines-Integrated Medicine(No.20150407)。 摘　　要：Liposomes hold great potential in anti-cancer drug delivery and the targeting treatment of tumors.However,the clinical therapeutic efficacy of liposomes is still limited by the complexity of tumor microenvironment(TME)and the insufficient accumulation in tumor sites.Meanwhile,the application of cholesterol and polyethylene glycol(PEG),which are usually used to prolong the blood circulation and stabilize the structure of liposomes respectively,has been questioned due to various disadvantages.Herein,we developed a ginsenoside Rh2-based multifunctional liposome system(Rh2-lipo)to effectively address these challenges once for all.Different with the conventional’wooden’liposomes,Rh2-lipo is a much more brilliant carrier with multiple functions.In Rh2-lipo,both cholesterol and PEG were substituted by Rh2,which works as membrane stabilizer,long-circulating stealther,active targeting ligand,and chemotherapy adjuvant at the same time.Firstly,Rh2 could keep the stability of liposomes and avoid the shortcomings caused by cholesterol.Secondly,Rh2-lipo showed a specifically prolonged circulation behavior in the blood.Thirdly,the accumulation of the liposomes in the tumor was significantly enhanced by the interaction of glucose transporter of tumor cells with Rh2.Fourth,Rh2-lipo could remodel the structure and reverse the immunosuppressive environment in TME.When tested in a 4T1 breast carcinoma xenograft model,the paclitaxel-loaded Rh2-lipo realized high efficient tumor growth suppression.Therefore,Rh2-lipo not only innovatively challenges the position of cholesterol as a liposome component,but also provides another innovative potential system with multiple functions for anti-cancer drug delivery. 关 键 词：Ginsenoside Rh2 Liposomes CHOLESTEROL MULTIFUNCTION Tumor targeting
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