EpCAM-Antibody-Labeled Noncytotoxic Polymer Vesicles for Cancer Stem Cells-Targeted Delivery of Anticancer Drug and siRNA
EpCAM-Antibody-Labeled Noncytotoxic Polymer Vesicles for Cancer Stem Cells-Targeted Delivery of Anticancer Drug and siRNA
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EpCAM-抗体标记的非细胞毒性聚合物囊泡用于癌症干细胞-抗癌药物和 siRNA 的靶向递送
DOI：
10.1021/acs.biomac.5b00551
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发表时间：
2015-06-01
影响因子：
6.2
通讯作者：
Du, Jianzhong
中科院分区：
文献类型：
--
作者：
Chen, Jing;Liu, Qiuming;Du, Jianzhong
癌症干细胞（CSC）具有启动肿瘤、维持肿瘤生长、维持肿瘤异质性的能力，并且由于其自我更新和多谱系分化能力以及对细胞毒药物的先天抵抗力而与化疗失败密切相关。在此，我们设计并合成了一种新型抗EpCAM（上皮细胞粘附分子）单克隆抗体标记的CSCs靶向、无细胞毒性和pH敏感的嵌段共聚物囊泡，作为抗癌药物和siRNA（通过沉默癌基因的表达来克服CSCs耐药性）的纳米载体。该囊泡显示出抗癌药物盐酸阿霉素（DOX 中心点 HCl）和 siRNA 向 CSC 的高递送效率，因为它被针对 CSC 表面特异性标记物的单克隆抗体标记。与非CSCs靶向囊泡相比，DOX中心点HCl或siRNA负载的CSCs靶向囊泡表现出更好的CSCs杀伤和肿瘤生长抑制能力，对正常细胞的毒性更低（IC50，DOX降低80％），展示了在纳米医学中的潜在应用前景。
Cancer stem cells (CSCs) have the capability to initiate tumor, to sustain tumor growth, to maintain the heterogeneity of tumor, and are closely linked to the failure of chemotherapy due to their self-renewal and multilineage differentiation capability with an innate resistance to cytotoxic agents. Herein, we designed and synthesized a novel anti-EpCAM (epithelial cell adhesion molecule)-monoclonal-antibody-labeled CSCs-targeting, noncytotoxic and pH-sensitive block copolymer vesicle as a nanocarrier of anticancer drug and siRNA (to overcome CSCs drug resistance by silencing the expression of oncogenes). This vesicle shows high delivery efficacy of both anticancer drug doxorubicin hydrochloride (DOX center dot HCl) and siRNA to the CSCs because it is labeled by the monoclonal antibodies to the CSCs-surface-specific marker. Compared to non-CSCs-targeting vesicles, the DOX center dot HCl or siRNA loaded CSCs-targeting vesicles exhibited much better CSCs killing and tumor growth inhibition capabilities with lower toxicity to normal cells (IC50,DOX decreased by 80%), demonstrating promising potential applications in nanomedicine.