A light-triggerable formulation to control the stability of pro-angiogenic transcription factor hypoxia inducible factor-1α (HIF-1α). Issue 18 (30th April 2020)

• Record Type: Journal Article
• Authors: Blersch, Josephine; Francisco, Vitor; Rebelo, Catarina; Jiménez-Balsa, Adrian; Antunes, Helena; Pinto, Sandra; Simões, Susana; Rai, Akhilesh; Ferreira, Lino
• Is Part Of: Nanoscale. Volume 12:Issue 18(2020)
• Page Start: 9935
• Page End: 9942
• Publication Date: 2020-04-30
• Subjects: Nanoscience -- Periodicals; Nanotechnology -- Periodicals; 620.505
• DOI: 10.1039/c9nr10503d
• Languages: English
• ISSNs: 2040-3364

Abstract

Abstract : Combining nanoparticle physico-chemical diversity and light responsiveness for the delivery of siRNAs to regulate transcription factor HIF-1α. Abstract : 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.