Enhanced glioma-targeting and stability of GICP peptide coupled with stabilized peptide A7R.
10.1016/j.apsb.2017.11.004
- Author:
Mingfei ZHANG
1
;
Weiyue LU
1
Author Information
1. Department of Pharmaceutics, School of Pharmacy, and Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, Shanghai 201203, China.
- Publication Type:Journal Article
- Keywords:
Blood–tumor barrier;
Glioma;
Neovasculature;
Peptide;
Stabilization;
Target
- From:
Acta Pharmaceutica Sinica B
2018;8(1):106-115
- CountryChina
- Language:English
-
Abstract:
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 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 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 barrier (BTB) was also determined. The results indicate that the coupled Y-shaped peptide A7R-GICP exhibited improved tumor and neovasculature targeting ability and had higher efficiency in crossing the BTB than either individual peptide.
