Efficient tumor targeting of hydroxycamptothecin loaded PEGylated niosomes modified with transferrin
Efficient tumor targeting of hydroxycamptothecin loaded PEGylated niosomes modified with transferrin
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转铁蛋白修饰的负载羟基喜树碱的聚乙二醇化脂质体的有效肿瘤靶向
DOI：
10.1016/j.jconrel.2008.09.005
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发表时间：
2009-01-19
影响因子：
10.8
通讯作者：
Pei, Yuanying
中科院分区：
文献类型：
--
作者：
Hong, Minghuang;Zhu, Saijie;Pei, Yuanying
以羟基喜树碱（HCPT）为模型药物，探讨聚乙二醇氰基丙烯酸酯-聚十六烷基氰基丙烯酸酯（PEG-PHDCA）修饰的囊泡的隐形作用和转铁蛋白受体介导的内吞作用对转铁蛋白（Tf）主动靶向作用的结合，促进药物在实体瘤中的靶向给药。采用薄膜水化法和超声法制备了载羟基喜树碱（HCPT）的聚乙二醇（PEG）囊泡（PEG-NS），将高碘酸氧化的Tf偶联到PEG的末端氨基上，制备了平均粒径为116 nm的活性靶向囊泡。KB细胞对Tf-PEG-NS的摄取呈浓度和时间依赖性。低温和游离Tf均能抑制胞吞作用，说明胞吞过程是能量驱动的，具有受体特异性。与HCPT注射液、非隐形囊泡和PEG-NS相比，Tf-PEG-NS对3种肿瘤细胞株的细胞毒作用最强（KB、K562和S180细胞），最大的细胞内摄取，尤其是在细胞核中，最高的肿瘤浓度和最大的肿瘤内羟基喜树碱浓度曲线下面积，对小鼠S180肿瘤的抑制率为71%。结果表明，转铁蛋白修饰的聚乙二醇化泡囊有望成为抗肿瘤药物靶向治疗的有效途径之一。(C)2008 Elsevier B. V.保留所有权利。
The aim of the present report was to exploit the possibility of combination of the stealth action by polyethylene glycol cyanoacrylate-co-hexadecyl cyanoacrylate (PEG-PHDCA) modified niosomes and active targeting function of transferrin (Tf) by transferrin receptor-mediated endocytosis to promote drug delivery to solid tumor following intravenous administration with hydroxycamptothecin (HCPT) as model drug. HCPT-loaded PEG-niosomes (PEG-NS) were prepared by thin-film hydration and ultrasound method; the periodate-oxidated Tf was coupled to terminal amino group of PEG to produce the active targeting vesicles with average diameters of 116 nm. The uptake of Tf-PEG-NS into KB cells was concentration and time dependent. which Could be inhibited by low temperature and free Tf, indicating that the endocytosis process was energy-driven and receptor specific. Compared with HCPT injection, non-stealth niosomes and PEG-NS, Tf-PEG-NS demonstrated the strongest cytotoxicity to three carcinomatous cell lines (KB, K562 and S180 cells), the greatest intracellular uptake especially in nuclei, the highest tumor concentration and largest area under the intratumoral hydroxycamptothecin concentration curve, as well as the most powerful anti-tumor activity with the inhibition rate of 71% against S180 tumor in mice. The results showed that the transferrin modified PEGylated niosomes Could be one of the promising solutions to the delivery of anti-tumor drugs to tumor. (C) 2008 Elsevier B.V. All rights reserved.