A light-triggerable nanoparticle library for the controlled release of non-coding RNAs

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 tri...

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Detalhes bibliográficos
Autor principal: Josephine, Blersch (author)
Outros Autores: Vitor, Francisco (author), Rebelo, Catarina (author), Adrian, Jimenez-Balsa (author), Antunes, Helena (author), Carlo, Gonzato (author), Pinto, Sandra (author), Simões, Susana (author), Klaus, Liedl (author), Karsten, Haupt (author), Ferreira, Lino (author)
Formato: article
Idioma:eng
Publicado em: 2019
Texto completo:http://hdl.handle.net/10316/88171
País:Portugal
Oai:oai:estudogeral.sib.uc.pt:10316/88171
Descrição
Resumo: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.