The pH-dependent association with cancer cells of tunable functionalized lipid vesicles with encapsulated doxorubicin for high cell-kill selectivity
The pH-dependent association with cancer cells of tunable functionalized lipid vesicles with encapsulated doxorubicin for high cell-kill selectivity
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DOI：
10.1016/j.biomaterials.2010.01.064
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发表时间：
2010-05-01
期刊：
影响因子：
14
通讯作者：
Sofou, Stavroula
中科院分区：
文献类型：
--
作者：
Karve, Shrirang;Bandekar, Amey;Sofou, Stavroula
为了实现选择性细胞杀伤，我们设计了功能化的脂质囊泡与pH触发的异质膜和封装阿霉素，表现出可调的表面形貌。这些囊泡在血液循环过程中从其表面“隐藏”（掩蔽）靶向配体，并且随着它们逐渐更深地渗透到肿瘤细胞中，仅逐渐“暴露”这些配体，其中在胞吞作用之后，它们爆发释放其内容物。激活结合反应性的刺激是血流（pH 7.4-7.0）和肿瘤内逐渐变酸的pH（pH 6.7-6.5）之间的pH梯度。多柔比星释放在内体pH 5.5-5.0下被激活。我们发现，可调功能化囊泡表现出环境依赖性（pH依赖性）与癌细胞的关联，导致高细胞杀伤选择性。当将细胞外pH从7.4降低至6.5时，可调功能化囊泡将阿霉素递送至癌细胞，其从最大值的41%增加至93%，从而分别导致癌细胞杀伤从最大值的23%增加至71%。这一概念验证显示了可调靶向脂质体化疗以环境依赖性方式选择性杀死癌细胞的潜力。(C)2010爱思唯尔有限公司版权所有。
To enable selective cell-kill, we designed functionalized lipid vesicles with pH-triggered heterogeneous membranes and encapsulated doxorubicin that exhibit tunable surface topography. These vesicles "hide" (mask) the targeting ligands from their surface during circulation in the blood, and only progressively "expose" these ligands as they gradually penetrate deeper into the tumor interstitium, where after endocytosis they burst release their contents. The stimulus to activate the binding reactivity is the pH gradient between the blood stream (pH 7.4-7.0) and the increasingly acidic pH inside the tumor interstitium (pH 6.7-6.5). Doxorubicin release is activated at the endosomal pH 5.5-5.0. We show that tunable functionalized vesicles exhibit environmentally-dependent (pH-dependent) association with cancer cells resulting in high cell-kill selectivity. When lowering the extracellular pH from 7.4 to 6.5, tunable functionalized vesicles deliver doxorubicin to cancer cells that increases from 41% to 93% of maximum resulting in cancer cell killing that increases from 23 to 71% of maximum, respectively. This proof-of-concept shows the potential of tunable targeted liposomal chemotherapy to selectively kill cancer cells in an environmentally-dependent way. (C) 2010 Elsevier Ltd. All rights reserved.