A Light-Triggerable Nanoparticle Library for the Controlled Release of Non-Coding RNAs
A Light-Triggerable Nanoparticle Library for the Controlled Release of Non-Coding RNAs
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DOI：
10.1002/anie.201911398
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发表时间：
2019-12-20
影响因子：
16.6
通讯作者：
Ferreira, Lino
中科院分区：
文献类型：
--
作者：
Blersch, Josephine;Francisco, Vitor;Ferreira, Lino
基于 RNA 的疗法提供了广泛的治疗干预措施，包括皮肤病的治疗；然而，由于细胞摄取和细胞质递送相关的障碍，有效递送这些生物分子的策略仍然受到限制。在此，我们报告了由 160 种配方组成的可触发聚合物纳米颗粒 (NP) 库的合成，呈现出物理化学多样性和对光的不同响应性。六种制剂在基因敲低活性方面比市售的 lipofectamine 更有效（高达 500%）。这些制剂显示出皮肤细胞的差异内化，并且内体逃逸很快（分钟范围）。 NPs 可有效释放 siRNA 和 miRNA。用与 miRNA-150-5p 复合的顶级 NP 治疗的急性皮肤伤口比用乱序 miRNA 治疗的伤口愈合得更快。光激活纳米颗粒提供了一种局部递送非编码 RNA 的新策略。
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.