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-t...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.展开更多
基金supported by National Basic Research Program of China (973 Program, No. 2013CB932500)National Natural Science Foundation of China (Nos. 81773657, 81690263 and 81473149)+1 种基金Shanghai Education Commission Major Project (No. 2017-01-07-00-07-E00052)Shanghai International Science and Technology Cooperation Project (No.16430723800)
文摘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.
