1. Hyaluronic acid-endostatin2-alft1 (HA-ES2-AF) nanoparticle-like conjugate for the target treatment of diseases.
- Author
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Sun F, Yu Y, Yang Z, Wang Z, Li Y, Wang F, and Tan H
- Subjects
- Animals, Cell Line, Chick Embryo, Chorioallantoic Membrane drug effects, Chorioallantoic Membrane physiology, Female, Mice, Nude, Rats, Wistar, Antineoplastic Agents administration & dosage, Endostatins administration & dosage, Hyaluronic Acid administration & dosage, Nanoparticles administration & dosage, Neoplasms drug therapy, Neovascularization, Pathologic drug therapy, Peptide Fragments administration & dosage, Vascular Endothelial Growth Factor Receptor-1 antagonists & inhibitors
- Abstract
Anti-flt1 peptide (GNQWFI, AF) specifically binds to Vascular Endothelial Growth Factor Receptor 1 (VEGFR1), thereby inhibiting the interaction of VEGFR1 with a series of ligands. ES2 (IVRRADRAAVP) can effectively inhibit the proliferation and invasion of endothelial cells and play a key role in anti-angiogenesis. AF and ES2 peptides differ in their activity. To better exploit the advantages of both, we designed a new peptide called ES2-AF (IVRRADRAAVPGGGGGGNQWFI). Hyaluronic acid (HA) is widely used in the pharmaceutical industry because of its biodegradable and high load performance. The HA-specific cell surface receptor CD44 was highly expressed in the tumour site during the anti-tumour study. Therefore, we used HA as a modifier to chemically modify ES2-AF; it was expected that the modified compound would have preferable solubility, stronger targeting, longer half-life, and better anti-angiogenesis effects in vivo. In this study, the anti-proliferative, anti-migration and targeting activities of HA-ES2-AF in vitro were studied by MTT, ELISA, transwell and SPR assays. Meanwhile, the anti-neovascularization activity of HA-ES2-AF in vivo was studied by CAM assay, and the targeting of HA-ES2-AF to tumour tissue was studied by bioimaging techniques. Finally, we also studied the half-life of HA-ES2-AF in vivo. In short, the bioactivity of the new peptide ES2-AF was enhanced to a certain extent, and ES2-AF modified by HA had higher anti-neovascularization activity in vitro and in vivo, had stronger targeting to tumour tissue, and had a significantly prolonged half-life in vivo. These results laid the foundation for its further development into targeting anti-tumour drugs., (Copyright © 2018 Elsevier B.V. All rights reserved.)
- Published
- 2018
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