Synergistic tumor microenvironment targeting and blood–brain barrier penetration via a pH-responsive dual-ligand strategy for enhanced breast cancer and brain metastasis therapy

Publication date: August 2018Source: Nanomedicine: Nanotechnology, Biology and Medicine, Volume 14, Issue 6Author(s): Man Li, Kairong Shi, Xian Tang, Jiaojie Wei, Xingli Cun, Yang Long, Zhirong Zhang, Qin HeAbstractCancer 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.Graphical AbstractAcid cleavable FA and dNP2 peptide co-modified PTX-loaded liposomes (cFd-Lip/PTX) exhibited synergistic TME targeting and BBB penetration. Firstly, FA ligand mediated the tumor targ...
Source: Nanomedicine: Nanotechnology, Biology and Medicine - Category: Nanotechnology Source Type: research