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Hyaluronic acid-endostatin2-alft1 (HA-ES2-AF) nanoparticle-like conjugate for the target treatment of diseases.
- Source :
-
Journal of Controlled Release . Oct2018, Vol. 288, p1-13. 13p. - Publication Year :
- 2018
-
Abstract
- 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. Graphical abstract Unlabelled Image [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 01683659
- Volume :
- 288
- Database :
- Academic Search Index
- Journal :
- Journal of Controlled Release
- Publication Type :
- Academic Journal
- Accession number :
- 132095287
- Full Text :
- https://doi.org/10.1016/j.jconrel.2018.08.038