Design and screening of a novel neuropilin-1 targeted penetrating peptide for anti-angiogenic therapy in glioma
| Autor: | Chunqian Zhao, Lei Wang, Xinke Zhang, Christina V. Malichewe, Xiu-Li Guo, Lin Zhao, Hongyuan Chen, Lu Lu |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Vascular Endothelial Growth Factor A
0301 basic medicine China Angiogenesis Mice Nude Angiogenesis Inhibitors Peptide 030226 pharmacology & pharmacy General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Drug Delivery Systems 0302 clinical medicine In vivo Cell Line Tumor Glioma Neuropilin 1 Human Umbilical Vein Endothelial Cells medicine Animals Humans General Pharmacology Toxicology and Pharmaceutics Tube formation chemistry.chemical_classification Mice Inbred BALB C Chemistry Endothelial Cells General Medicine medicine.disease Vascular Endothelial Growth Factor Receptor-2 Neuropilin-1 In vitro Cell biology 030104 developmental biology Blood-Brain Barrier Liposomes Drug delivery Female Immunotherapy Drug Screening Assays Antitumor Peptides Signal Transduction |
| Zdroj: | Life Sciences. 270:119113 |
| ISSN: | 0024-3205 |
| Popis: | Aims This study aimed to design and screen a dual functional fusion peptide that could penetrate the blood-brain barrier and target neuropilin 1 (NRP1) overexpressed in vascular endothelial cells for the anti-angiogenesis of glioma treatment. Main methods At the cellular level, the in vitro anti-angiogenic activity of six NRP1 targeting peptides was screened by testing the ability to inhibit the proliferation and tube formation of HUVECs. Then, the in vitro anti-angiogenic activity of two fusion peptides containing different linkers was screened by testing the ability to inhibit HUVECs proliferation, tube formation and migration. The effect of fusion peptide on VEGFR2 related signal pathway was confirmed by Western-blotting. Surface plasmon resonance technology was used to detect the affinity of the fusion peptide to NRP1. The ability of FITC-labeled peptides to penetrate cells was confirmed by cell uptake assay. By establishing an orthotopic glioma model, we evaluated the ability of FITC-labeled peptides to penetrate the blood-brain barrier and their anti-glioma growth activity in vivo. Key findings We found that NRP1 targeting peptide RP7 and linker cysteine were the most suitable key components in the fusion peptide. We also found that the fusion peptide Tat-C-RP7 we constructed had the strongest ability to penetrate the blood-brain barrier and anti-angiogenic activity in vitro and in vivo. Significance At present, NRP1 targeting peptide as a drug delivery tool and molecular probe seems to have received more attention. We constructed a fusion peptide Tat-C-RP7 with strong anti-angiogenic activity for the treatment of glioma. |
| Databáze: | OpenAIRE |
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