转移
癌症研究
肿瘤微环境
乳腺癌
血脑屏障
癌症
三阴性乳腺癌
脑转移
癌细胞
肽
医学
化学
内科学
中枢神经系统
生物化学
肿瘤细胞
作者
Man Li,Kai Shi,Xian Tang,Jiafu Wei,Xingli Cun,Yang Long,Zhirong Zhang,Qin He
标识
DOI:10.1016/j.nano.2018.05.008
摘要
Cancer associated fibroblasts (CAFs) which shape the tumor microenvironment (TME) and the presence of blood brain barrier (BBB) remain great challenges in targeting breast cancer and its brain metastasis. Herein, we reported a strategy using PTX-loaded liposome co-modified with acid-cleavable folic acid (FA) and BBB transmigrating cell penetrating peptide dNP2 peptide (cFd-Lip/PTX) for enhanced delivery to orthotopic breast cancer and its brain metastasis. Compared with single ligand or non-cleavable Fd modified liposomes, cFd-Lip exhibited synergistic TME targeting and BBB transmigration. Moreover, upon arrival at the TME, the acid-cleavable cFd-Lip/PTX showed sensitive cleavage of FA, which reduced the hindrance effect and maximized the function of both FA and dNP2 peptide. Consequently, efficient targeting of folate receptor (FR)-positive tumor cells and FR-negative CAFs was achieved, leading to enhanced anti-tumor activity. This strategy provides a feasible approach to the cascade targeting of TME and BBB transmigration in orthotopic and metastatic cancer treatment.
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