Preparation and evaluation of paclitaxel-loaded PEGylated immunoliposome
Preparation and evaluation of paclitaxel-loaded PEGylated immunoliposome
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DOI：
10.1016/j.jconrel.2007.05.011
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发表时间：
2007-07-31
影响因子：
10.8
通讯作者：
Kim, Dae-Duk
中科院分区：
文献类型：
--
作者：
Yang, Tao;Choi, Min-Koo;Kim, Dae-Duk
开发了一种针对人乳腺癌细胞定制的空间稳定的负载紫杉醇的脂质体，从而通过受体介导的内吞作用提高紫杉醇的细胞内递送效率。结果表明，靶向部分（硫醇化赫赛汀）成功偶联至聚乙二醇-磷脂缀合物的远端反应性马来酰亚胺末端，并并入脂质体双层中。聚乙二醇化免疫脂质体的粒径保持在约200nm。共聚焦显微镜研究表明，聚乙二醇化免疫脂质体通过受体介导的胞吞途径被摄取到肿瘤细胞内部。在 37°C 过表达人表皮生长因子受体 2 (HER2) 的癌细胞（BT-474 和 SK-BR-3）中，聚乙二醇化免疫脂质体的细胞摄取量明显高于聚乙二醇化脂质体，而在低 HER2 表达细胞 (MDA-MB-23 1) 和低温 (4°C) 下均未发现差异。将紫杉醇在聚乙二醇化免疫脂质体中的药代动力学与紫杉醇((R)) 和聚乙二醇化脂质体中的药代动力学进行了比较。紫杉醇在聚乙二醇化免疫脂质体中的循环时间比紫杉醇延长，但比聚乙二醇化脂质体中的循环时间稍短。因此，使用赫赛汀的负载紫杉醇的聚乙二醇化免疫脂质体可以作为未来 HER2 过表达乳腺癌的肿瘤特异性癌症治疗的有前途的模型。 (c) 2007 Elsevier B.V. 保留所有权利。
A sterically stabilized paclitaxel-loaded liposome tailored to target human breast cancer cells was developed, thereby promoting the efficiency of intracellular delivery of paclitaxel through receptor-mediated endocytosis. Results indicated that the targeting moiety (thiolated Herceptin) was Successfully coupled to the distal reactive maleimide terminus of the poly (ethylene glycol)-phospholipid conjugate as well as being incorporated 9 in the liposonial bilayers. The particle size of the PEGylated immunoliposome was maintained at about 200 nm. Confocal microscopy studies showed that the PEGylated immunoliposome was uptaken into the interior of the tumor cell through the receptor-mediated enclocytosis pathway. The PEGylated immunoliposome showed substantially higher cellular uptake than the PEGylated liposome in cancer cells (BT-474 and SK-BR-3) over-expressing human epidermal growth factor receptor 2 (HER2) at 37 degrees C, while no difference was found in low HER2 expressing cells (MDA-MB-23 1) nor at low temperature (4 degrees C). Pharmacokinetics of paclitaxel in the PEGylated immunoliposome was compared with that in Taxol((R)) and in the PEGylated liposome in rats. The circulating time of paclitaxel in the PEGylated immunoliposome was prolonged compared to Taxol((R)) while slightly shortened than that in the PEGylated liposome. Therefore, the paclitaxel-loaded PEGylated imummoliposome using Herceptin could serve as a promising model for future tumor specific cancer therapy of HER2 over-expressing breast cancers. (c) 2007 Elsevier B.V. All rights reserved.