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Title: A light-triggerable nanoparticle library for the controlled release of non-coding RNAs
Authors: Josephine, Blersch
Vitor, Francisco
Catarina, Rebelo
Adrian, Jimenez-Balsa
Helena, Antunes
Carlo, Gonzato
Sandra, Pinto
Susana, Simões
Klaus, Liedl
Karsten, Haupt
Lino, Ferreira
Issue Date: 14-Nov-2019
Publisher: Wiley
Project: ERA Chair project (ERA@UC, ref:669088) through EU Horizon 2020 program, the POCI-01-0145-FEDER-016390 (acronym: CANCEL STEM) and POCI-01- 0145-FEDER-029414 (acronym: LIghtBRARY) projects through Compete 2020 and FCT programs. NMR data was collected at the UC-NMR facility which is supported in part by FEDER – European Regional Development Fund through the COMPETE Programme (Operational Programme for Competitiveness) and by National Funds through FCT – Fundação para a Ciência e a Tecnologia (Portuguese Foundation for Science and Technology) through grants REEQ/481/QUI/2006, RECI/QEQ-QFI/0168/2012, CENTRO-07-CT62- FEDER-002012, and Rede Nacional de Ressonância Magnética Nuclear (RNRMN). 
Serial title, monograph or event: Angewandte Chemie International Edition
Abstract: RNA-based therapies offer a wide range of therapeutic interventions including for the treatment of skin diseases; however, the strategies to deliver efficiently these biomolecules are still limited due to obstacles related to the cellular uptake and cytoplasmic delivery. Herein, we synthesized a triggerable polymeric nanoparticle (NP) library composed by 160 formulations, presenting physico-chemical diversity and differential responsiveness to light. Six formulations were more efficient (up to 500%) than commercial Lipofectamine in gene knockdown activity. These formulations had differential internalization by skin cells and the endosomal escape was rapid (minutes range) as shown by the recruitment of galectin-8. The NPs were effective in the release of siRNA and miRNA. Acute skin wounds treated with the top hit NP complexed with miRNA-150-5p healed faster than wounds treated with scramble miRNA. Light-activatable NPs offer a new strategy to deliver topically non-coding RNAs.
DOI: 10.1002/anie.201911398
Rights: openAccess
Appears in Collections:I&D CNC - Artigos em Revistas Internacionais

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