A Light-Triggerable Nanoparticle Library for the Controlled Release of Non-Coding RNAs

被引：24

作者：

Blersch, Josephine ^{[1
]}

Francisco, Vitor ^{[1
,2
]}

Rebelo, Catarina ^{[1
,2
]}

Jimenez-Balsa, Adrian ^{[1
]}

Antunes, Helena ^{[1
,2
]}

Gonzato, Carlo ^{[3
]}

Pinto, Sandra ^{[1
]}

Simoes, Susana ^{[1
]}

Liedl, Klaus ^{[4
]}

Haupt, Karsten ^{[3
]}

Ferreira, Lino ^{[1
,2
]}

机构：

[1] Univ Coimbra, Ctr Neurosci & Cell Biol, Coimbra, Portugal

[2] Univ Coimbra, Fac Med, P-3000548 Coimbra, Portugal

[3] Univ Technol Compiegne, Sorbonne Univ, Lab Enzyme & Cell Engn, UMR 7025,CNRS, F-60200 Compiegne, France

[4] Leopold Franzens Univ, Fac Chem & Pharm, Innsbruck, Austria

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2020年 / 59卷 / 05期

基金：

欧盟地平线“2020”;

关键词：

high-throughput screening; non-coding RNA; nanoparticles; polymers; RNA delivery; SIRNA DELIVERY; OLIGONUCLEOTIDE;

D O I：

10.1002/anie.201911398

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

RNA-based therapies offer a wide range of therapeutic interventions including the treatment of skin diseases; however, the strategies to efficiently deliver these biomolecules are still limited due to obstacles related to the cellular uptake and cytoplasmic delivery. Herein, we report the synthesis of a triggerable polymeric nanoparticle (NP) library composed of 160 formulations, presenting physico-chemical diversity and differential responsiveness to light. Six formulations were more efficient (up to 500 %) than commercially available lipofectamine in gene-knockdown activity. These formulations showed differential internalization by skin cells and the endosomal escape was rapid (minutes range). 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 scrambled miRNA. Light-activatable NPs offer a new strategy to topically deliver non-coding RNAs.

引用

页码：1985 / 1991

页数：7

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