Somatostatin receptor-mediated tumor-targeting drug delivery using octreotide-PEG-deoxycholic acid conjugate-modified N-deoxycholic acid-O, N-hydroxyethylation chitosan micelles
Somatostatin receptor-mediated tumor-targeting drug delivery using octreotide-PEG-deoxycholic acid conjugate-modified N-deoxycholic acid-O, N-hydroxyethylation chitosan micelles
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使用奥曲肽-PEG-脱氧胆酸缀合物修饰的 N-脱氧胆酸-O,N-羟乙基化壳聚糖胶束进行生长抑素受体介导的肿瘤靶向药物递送
DOI：
10.1016/j.biomaterials.2012.05.052
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发表时间：
2012-09-01
期刊：
影响因子：
14
通讯作者：
Zhang, Qiang
中科院分区：
文献类型：
--
作者：
Huo, Meirong;Zou, Aifeng;Zhang, Qiang
在本研究中，成功合成了配体-PEG-脂质缀合物奥曲肽-聚乙二醇-脱氧胆酸（OCT(Phe)-PEG-DOCA，或OPD），并将其用作N-脱氧胆酸-O，N-羟乙基化壳聚糖（DAHC）胶束的靶向分子，用于有效的癌症治疗。 DAHC胶束对模型抗癌药物阿霉素（DOX）表现出良好的负载能力，OPD的修饰对载药量没有明显影响，同时略微增大了粒径并部分屏蔽了胶束表面的正电荷。 OPD 修饰后，还观察到 DOX 从胶束中的释放速率加快，并且释放曲线表现出 pH 敏感特性。与DAHC-DOX胶束相比，OPD-DAHC-DOX胶束对MCF-7细胞（SSTRs过表达）表现出明显更强的细胞毒性，但与WI-38细胞（无SSTRs表达）几乎没有任何差异。流式细胞术和共聚焦激光扫描显微镜的结果进一步表明OPD-DAHC-DOX胶束可以通过SSTR介导的内吞作用选择性地进入肿瘤细胞。对携带 MCF-7 癌症异种移植物的裸鼠胶束的体内研究证实，OPD-DAHC 胶束比 DAHC 对照具有更高的肿瘤靶向能力，并表现出增强的抗肿瘤功效和降低的全身毒性。这些结果表明 OPD-DAHC 胶束可能是一种有前景的用于癌症靶向治疗的抗癌药物递送载体。 (c) 2012 Elsevier Ltd. 保留所有权利。
In this study, a ligand-PEG-lipid conjugate, octreotide-polyethene glycol-deoxycholic acid (OCT(Phe)-PEG-DOCA, or OPD) was successfully synthesized and used as a targeting molecule for N-deoxycholic acid-O, N-hydroxyethylation chitosan (DAHC) micelles for efficient cancer therapy. DAHC micelles exhibited good loading capacities for doxorubicin (DOX), a model anti-cancer drug, and the modification of OPD showed no significant effect on drug load while slightly increasing the particle size and partly shielding the positive charges on the surface of micelles. Accelerated release rate of DOX from micelles were also observed after OPD modification and the release profile exhibited pH-sensitive properties. Compared with DAHC-DOX micelles, OPD-DAHC-DOX micelles exhibited significantly stronger cytotoxicity to MCF-7 cells (SSTRs overexpression) but with hardly any difference from WI-38 cells (no SSTRs expression). The results of flow cytometry and confocal laser scanning microscopy further revealed that OPD-DAHC-DOX micelles could be selectively taken into tumor cells by SSTRs-mediated endocytosis. In vivo investigation of micelles on nude mice bearing MCF-7 cancer xenografts confirmed that OPD-DAHC micelles possessed much higher tumor-targeting capacity than the DAHC control and exhibited enhanced anti-tumor efficacy and decreased systemic toxicity. These results suggest that OPD-DAHC micelles might be a promising anti-cancer drug delivery carrier for targeted cancer therapy. (c) 2012 Elsevier Ltd. All rights reserved.