Local anti-angiogenic therapy by magnet-assisted downregulation of SHP2 phosphatase
| Autor: | Alexandra Heidsieck, Hanna Mannell, Yvonn Heun, Olga Mykhaylyk, Sarah Rieck, Daniela Wenzel, Bernhard Gleich, Alexander Pfeifer |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Angiogenesis
Genetic enhancement Phosphatase Genetic Vectors Pharmaceutical Science Down-Regulation Neovascularization Physiologic Protein Tyrosine Phosphatase Non-Receptor Type 11 02 engineering and technology Protein tyrosine phosphatase Cell Line 03 medical and health sciences Mice Downregulation and upregulation In vivo RNA interference Transduction Genetic Animals 030304 developmental biology 0303 health sciences Neovascularization Pathologic Chemistry Lentivirus Mouse Embryonic Stem Cells 021001 nanoscience & nanotechnology Embryonic stem cell Cell biology Magnets RNA Interference 0210 nano-technology |
| Zdroj: | Journal of controlled release : official journal of the Controlled Release Society. 305 |
| ISSN: | 1873-4995 |
| Popis: | Anti-angiogenic therapies are promising options for diseases with enhanced vessel formation such as tumors or retinopathies. In most cases, a site-specific local effect on vessel growth is required, while the current focus on systemic distribution of angiogenesis inhibitors may cause severe unwanted side-effects. Therefore, in the current study we have developed an approach for the local inhibition of vascularization, using complexes of lentivirus and magnetic nanoparticles in combination with magnetic fields. Using this strategy in the murine embryonic stem cell (ESC) system, we were able to site-specifically downregulate the protein tyrosine phosphatase SHP2 by RNAi technology in areas with active vessel formation. This resulted in a reduction of vessel development, as shown by reduced vascular tube length, branching points and vascular loops. The anti-angiogenic effect could also be recapitulated in the dorsal skinfold chamber of mice in vivo. Here, site-specific downregulation of SHP2 reduced re-vascularization after wound induction. Thus, we have developed a magnet-assisted, RNAi-based strategy for the efficient local inhibition of angiogenesis in ESCs in vitro and also in vivo. |
| Databáze: | OpenAIRE |
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