Abstract
Cancer is the leading cause of death worldwide, and metastasis is the main attribute to cancer death. CXCR4 and its natural ligand CXCL12 have been known to play a critical role in tumorigenesis, angiogenesis and metastasis. Therefore, designing a new CXCR4 antagonist to prevent tumor metastasis will be of great significance. Herein, a novel chemically synthesized peptide (E5) that has an ability to target CXCR4/CXCL12 axis was loaded in micelle glycol-phosphatidylethanolamine (PEG-PE) block copolymer to form micelle-encapsulated E5 (M-E5). We demonstrated that M-E5 exhibited higher affinity for CXCR4-overexpressing MCF-7 and HepG2 tumor cells as compared to free E5, and efficiently inhibited the tumor cells migration. Mechanistic studies implied that PEG-PE micelle can encapsulate E5 and improve E5 targeting efficiency for CXCR4 by accumulating E5 on the tumor cell membrane. Furthermore, through encapsulation of chemotherapeutic drug doxorubicin (Dox) in PEG-PE micelle, we proved that PEG-PE micelle could serve as a co-carrier for both E5 and Dox (M-E5-Dox). M-E5 enhanced the efficiency of Dox by down-regulating the phosphorylation level of Akt, Erk and p38/MAPK proteins. In conclusion, PEG-PE micelle demonstrated a promising delivery system for E5, and M-E5 is expected to be a potential therapeutic agent that will help to improve the clinical benefits in current therapies used for solid tumors.