†Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Middle Yanchang Road, Shanghai 200072, China.
‡Key Laboratory of Advanced Civil Engineering Materials of Ministry of Education, School of Materials Science and Engineering, Tongji University, 4800 Caoan Road, Shanghai 201804, China.
Biomacromolecules. 2015 Jun 8;16(6):1695-705. doi: 10.1021/acs.biomac.5b00551. Epub 2015 May 28.
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·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·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.
癌症干细胞（CSCs）具有启动肿瘤、维持肿瘤生长、维持肿瘤异质性的能力，并由于其自我更新和多能分化能力以及对细胞毒性药物的固有抗性，与化疗失败密切相关。在这里，我们设计并合成了一种新型的抗 EpCAM（上皮细胞黏附分子）-单克隆抗体标记的 CSCs 靶向、非细胞毒性和 pH 敏感的嵌段共聚物囊泡作为抗癌药物和 siRNA 的纳米载体（通过沉默癌基因的表达来克服 CSCs 耐药性）。由于囊泡被标记为 CSCs 表面特异性标志物的单克隆抗体，因此该囊泡对 CSCs 具有很高的递药效率，同时递药效率也很高盐酸阿霉素（DOX·HCl）和 siRNA。与非 CSCs 靶向囊泡相比，负载 DOX·HCl 或 siRNA 的 CSCs 靶向囊泡对 CSCs 的杀伤和肿瘤生长抑制能力更强，对正常细胞的毒性更低（IC50，DOX 降低了 80%），在纳米医学中有很好的应用前景。
