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Cholesterol-tuned liposomal membrane rigidity directs tumor penetration and anti-tumor effect

文献类型：期刊论文

作者Wu, Hangyi1,2; Yu, Miaorong2; Miao, Yunqiu2; He, Shufang2; Dai, Zhuo2; Song, Wenyi2; Liu, Yuan2; Song, Sha2; Ahmad, Ejaj2; Wang, Dongkai1
刊名ACTA PHARMACEUTICA SINICA B
出版日期2019-07-01
卷号9期号:4页码:858-870
关键词Cholesterol Liposomal membrane rigidity Tumor penetration Anti-tumor effects
ISSN号2211-3835
DOI10.1016/j.apsh.2019.02.010
通讯作者Wang, Dongkai(wangycsyphu@126.com) ; Gan, Yong(ygan@simm.ac.cn)
英文摘要Recently, liposomes have been widely used in cancer therapeutics, but their anti-tumor effects are suboptimal due to limited tumor penetration. To solve this problem, researchers have made significant efforts to optimize liposomal diameters and potentials, but little attention has been paid to liposomal membrane rigidity. Herein, we sought to demonstrate the effects of cholesterol-tuned liposomal membrane rigidity on tumor penetration and anti-tumor effects. In this study, liposomes composed of hydrogenated soybean phospholipids (HSPC), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG(2000)) and different concentrations of cholesterol were prepared. It was revealed that liposomal membrane rigidity decreased with the addition of cholesterol. Moderate cholesterol content conferred excellent diffusivity to liposomes in simulated diffusion medium, while excessive cholesterol limited the diffusion process. We concluded that the differences of the diffusion rates likely stemmed from the alterations in liposomal membrane rigidity, with moderate rigidity leading to improved diffusion. Next, the in vitro tumor penetration and the in vivo anti-tumor effects were analyzed. The results showed that liposomes with moderate rigidity gained excellent tumor penetration and enhanced anti-tumor effects. These findings illustrate a feasible and effective way to improve tumor penetration and therapeutic efficacy of liposomes by changing the cholesterol content, and highlight the importance of liposomal membrane rigidity. (C) 2019 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences.
WOS关键词LIPID-COMPOSITION ; BENDING RIGIDITY ; NANOPARTICLES ; DELIVERY ; CANCER ; TEMPERATURE ; DIFFUSION ; MICELLES ; NANORODS ; THERAPY
资助项目National Natural Science Foundation of China[81573378] ; National Natural Science Foundation of China[81773651] ; Science and Technology Innovation Action Plan for Basic Research of Shanghai 2014 (China)[14JC1493200] ; Shanghai Sailing Program 2017 (China)[17YF1423500] ; K.C.Wong Education Foundation (China)
WOS研究方向Pharmacology & Pharmacy
语种英语
WOS记录号WOS:000476730700017
出版者INST MATERIA MEDICA, CHINESE ACAD MEDICAL SCIENCES
源URL[http://119.78.100.183/handle/2S10ELR8/289060]  
专题中国科学院上海药物研究所
通讯作者Wang, Dongkai; Gan, Yong
作者单位1.Shenyang Pharmaceut Univ, Dept Pharmaceut, Shenyang 117004, Liaoning, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, 501 Haike Rd, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Wu, Hangyi,Yu, Miaorong,Miao, Yunqiu,et al. Cholesterol-tuned liposomal membrane rigidity directs tumor penetration and anti-tumor effect[J]. ACTA PHARMACEUTICA SINICA B,2019,9(4):858-870.
APA Wu, Hangyi.,Yu, Miaorong.,Miao, Yunqiu.,He, Shufang.,Dai, Zhuo.,...&Gan, Yong.(2019).Cholesterol-tuned liposomal membrane rigidity directs tumor penetration and anti-tumor effect.ACTA PHARMACEUTICA SINICA B,9(4),858-870.
MLA Wu, Hangyi,et al."Cholesterol-tuned liposomal membrane rigidity directs tumor penetration and anti-tumor effect".ACTA PHARMACEUTICA SINICA B 9.4(2019):858-870.

入库方式： OAI收割

来源：上海药物研究所

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