Cholesterol-tuned liposomal membrane rigidity directs tumor penetration and anti-tumor effect
查看参考文献51篇
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文摘
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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. |
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来源
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Acta Pharmaceutica Sinica B
,2019,9(4):858-870 【核心库】
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DOI
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10.1016/j.apsb.2019.02.010
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关键词
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Cholesterol
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Liposomal membrane rigidity
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Tumor penetration
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Anti-tumor effects
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地址
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1.
Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang, 117004
2.
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203
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语种
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英文 |
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文献类型
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研究性论文 |
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ISSN
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2211-3835 |
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学科
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药学 |
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基金
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国家自然科学基金
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the Science and Technology Innovation Action Plan for Basic Research of Shanghai 2014
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Shanghai Sailing Program 2017
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文献收藏号
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CSCD:6552418
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