Tumor endothelial cell-specific drug delivery system using apelin-conjugated liposomes.
Tumor endothelial cell-specific drug delivery system using apelin-conjugated liposomes.
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DOI：
10.1371/journal.pone.0065499
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Takakura N
中科院分区：
文献类型：
--
作者：
Kawahara H;Naito H;Takara K;Wakabayashi T;Kidoya H;Takakura N
需要一种针对肿瘤内皮细胞(ECs)的药物传递系统来防止血管生成抑制剂对正常血管的破坏。本研究的目的是探讨血管生成时内皮细胞表达APJ的配体apelin是否可用于靶向向肿瘤内皮细胞输送药物。用TAMRA(荧光探针)标记的apelin研究了在NIH-3T3细胞中稳定表达的APJ对apelin的摄取。长和短两种形式的apelin(apelin 36和apelin 13)都被吸收，后者更有效。为了提高apelin-脂质体偶联物的有效性，我们在apelin 13的C末端引入了半胱氨酸及其巯基，从而产生了apelin 14。反过来，apelin 14被偶联到罗丹明脂质体上，并应用于荷瘤小鼠。在肿瘤微环境中，我们证实了脂质体已整合到内皮细胞的胞浆中。相反，内皮细胞胞浆中很少发现apelin非结合脂质体。此外，在其他正常器官中很少检测到apelin偶联脂质体的非特异性摄取。在正常器官中的内皮细胞几乎不表达APJ；然而，在低氧刺激下，例如在肿瘤中，内皮细胞开始表达APJ。目前的研究表明，apelin可能是一种合适的工具，可以有效地将药物特异性地输送到肿瘤内的内皮细胞。
A drug delivery system specifically targeting endothelial cells (ECs) in tumors is required to prevent normal blood vessels from being damaged by angiogenesis inhibitors. The purpose of this study was to investigate whether apelin, a ligand for APJ expressed in ECs when angiogenesis is taking place, can be used for targeting drug delivery to ECs in tumors. Uptake of apelin via APJ stably expressed in NIH-3T3 cells was investigated using TAMRA (fluorescent probe)-conjugated apelin. Both long and short forms of apelin (apelin 36 and apelin 13) were taken up, the latter more effectively. To improve efficacy of apelin- liposome conjugates, we introduced cysteine, with its sulfhydryl group, to the C terminus of apelin 13, resulting in the generation of apelin 14. In turn, apelin 14 was conjugated to rhodamine-encapsulating liposomes and administered to tumor-bearing mice. In the tumor microenvironment, we confirmed that liposomes were incorporated into the cytoplasm of ECs. In contrast, apelin non-conjugated liposomes were rarely found in the cytoplasm of ECs. Moreover, non-specific uptake of apelin-conjugated liposomes was rarely detected in other normal organs. ECs in normal organs express little APJ; however, upon hypoxic stimulation, such as in tumors, ECs start to express APJ. The present study suggests that apelin could represent a suitable tool to effectively deliver drugs specifically to ECs within tumors.
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影响因子：
50.5
作者：
O'Brien, MER;Wigler, N;Tendler, C
通讯作者：
Tendler, C
DOI：
10.1016/j.bbrc.2010.03.151
发表时间：
2010-04-30
影响因子：
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作者：
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作者：
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影响因子：
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作者：
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通讯作者：
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