Enhanced glioma-targeting and stability of LGICP peptide coupled with stabilized peptide DA7R

• 来源期刊: 药学学报（英文版）
• 关键词: Glioma Neovasculature Target Peptide Stabilization Blood-tumor barrier
• 年，卷（期）: 2018,（1）
• 页码范围: 106-115
• 页数: 10页
• 语种: 英文

摘要

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 DA7R 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 DA7R 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 DA7R-GICP exhibited improved tumor and neovasculature targeting ability and had higher efficiency in crossing the BTB than either individual peptide.