Malignant glioma is usually accompanied by vigorous angiogenesis to provide essential nutrients. An effective glioma targeting moiety should include excellent tumor-cell homing ability as well as good neovasculature-targeting efficiency, and should be highly resistant to enzyme degradation in the bloodstream. The phage display-selected heptapeptide, the glioma-initiating cell peptide (GICP), was previously reported as a ligand for the VAV3 protein (a Rho-GTPase guanine nucleotide exchange factor), which is mainly expressed on glioma cells; the stabilized heptapeptide (D)A7R has been shown to be the ligand of both vascular endothelial growth factor receptor 2 (VEGFR2) and neuropilin-1 (NRP-1), and has demonstrated good neovasculature-targeting ability. By linking (D)A7R and GICP, a multi-receptor targeting molecule was obtained. The stability of these three peptides was evaluated and their targeting efficiency on tumor-related cells and models was compared. The ability of these peptides to cross the blood tumor bather (BTB) was also determined. The results indicate that the coupled Y-shaped peptide (D)A7R GICP exhibited improved tumor and neovasculature targeting ability and had higher efficiency in crossing the BTB than either individual peptide. (C) 2018 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.
[1]Fudan Univ, Minist Educ, Sch Pharm, Dept Pharmaceut, Shanghai 201203, Peoples R China.
[2]Fudan Univ, Minist Educ, Key Lab Smart Drug Delivery, Shanghai 201203, Peoples R China.
[3]Fudan Univ, State Key Lab Med Neurobiol, Shanghai 200032, Peoples R China.
[4]Fudan Univ, Collaborat Innovat Ctr Brain Sci, Shanghai 200032, Peoples R China.
[5]Zhongshan Hosp, Minhang Branch, Shanghai 201199, Peoples R China.
[6]Fudan Univ, Minghang Hosp, Inst Fudan Minghang Acad Hlth Syst, Shanghai 201199, Peoples R China.
[7]Fudan Univ, Inst Integrat Med, Shanghai 200040, Peoples R China.
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