A light-triggerable formulation to control the stability of pro-angiogenic transcription factor hypoxia inducible factor-1α (HIF-1α)
| Autor: | Susana Simões, Lino Ferreira, Vitor Francisco, Akhilesh Rai, Catarina Rebelo, Sandra Pinto, Adrian Jiménez-Balsa, Helena Antunes, Josephine Blersch |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Small interfering RNA
Polymers Ultraviolet Rays Chemistry Pharmaceutical 02 engineering and technology Diamines Transfection Hypoxia-Inducible Factor-Proline Dioxygenases 03 medical and health sciences RNA interference Gene silencing Humans General Materials Science RNA Small Interfering Transcription factor 030304 developmental biology Cell Proliferation 0303 health sciences Gene knockdown Acrylamides Drug Carriers Chemistry Protein Stability Endothelial Cells 021001 nanoscience & nanotechnology Hypoxia-Inducible Factor 1 alpha Subunit 3. Good health Cell biology Hypoxia-inducible factors Lipofectamine Nanoparticles RNA Interference 0210 nano-technology |
| Zdroj: | Repositório Científico de Acesso Aberto de Portugal Repositório Científico de Acesso Aberto de Portugal (RCAAP) instacron:RCAAP Nanoscale |
| Popis: | The control of vascular remodeling mediated by transcription factor HIF-1α is critical in the treatment of several diseases including cancer, retinopathies, chronic wounds, and ischemic heart disease, among others. Gene silencing using a small interfering RNA (siRNA) is a promising therapeutic strategy to regulate HIF-1α; however, the delivery systems developed so far have limited endothelial targeting and efficiency. Herein, we have synthesized a light-triggerable polymeric nanoparticle (NP) library composed of 110 formulations which showed variable morphology, charge and disassembly rates after UV exposure. More than 35% of the formulations of the library were more efficient in gene knockdown than the siRNA delivered by a commercial transfection agent (lipofectamine RNAiMAX). The most efficient siRNA delivery formulations were tested against different cell types to identify one with preferential targeting to endothelial cells. Using a two-step methodology, we have identified a formulation that shows exquisite targeting to endothelial cells and is able to deliver more efficiently the siRNA that modulates HIF-1α than commercial transfection agents. Overall, the strategy reported here increases the specificity for tissue regulation and the efficiency for the intracellular delivery of siRNAs. |
| Databáze: | OpenAIRE |
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