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

IMR OpenIR

	Cholesterol-tuned liposomal membrane rigidity directs tumor penetration and anti-tumor effect
其他题名	Cholesterol-tuned liposomal membrane rigidity directs tumor penetration and anti-tumor effect
	Wu Hangyi 1; Yu Miaorong 2; Miao Yunqiu 2; He Shufang 2; Dai Zhuo 2; Song Wenyi 2; Liu Yuan 2; Song Sha 2; Ahmad Ejaj 2; Wang Dongkai 1; Gan Yong 2
	2019
发表期刊	Acta Pharmaceutica Sinica B
ISSN	2211-3835
卷号	9 期号:4 页码:858-870
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-PEG2000) 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. KEY WORDS: Cholesterol, Liposomal membrane rigidity, Tumor penetration, Anti-tumor effects
其他摘要	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.
关键词	Therapeutics. Pharmacology RM1-950
收录类别	CSCD
语种	英语
资助项目	[National Natural Science Foundation of China] ; [Science and Technology Innovation Action Plan for Basic Research of Shanghai 2014 (China)] ; [Shanghai Sailing Program 2017 (China)] ; [K.C.Wong Education Foundation (China)]
CSCD记录号	CSCD:6552418
引用统计	被引频次：6[CSCD] [CSCD记录]
文献类型	期刊论文
条目标识符	http://ir.imr.ac.cn/handle/321006/89805
专题	中国科学院金属研究所
作者单位	1.中国科学院金属研究所 2.中国科学院
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.