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

Josephine Blersch1, Vitor Francisco1,2, Catarina Rebelo1,2

  • 1Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.

Angewandte Chemie (International Ed. in English)
|November 16, 2019
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Summary

New light-activatable polymeric nanoparticles efficiently deliver RNA for gene knockdown and accelerate skin wound healing. These novel nanoparticles overcome cellular uptake and delivery challenges for RNA therapeutics.

Keywords:
RNA deliveryhigh-throughput screeningnanoparticlesnon-coding RNApolymers

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Area of Science:

  • Biotechnology
  • Nanomedicine
  • Dermatology

Background:

  • RNA-based therapies show promise for treating skin diseases.
  • Efficient delivery of RNA molecules to cells remains a significant challenge.
  • Current delivery methods face limitations in cellular uptake and cytoplasmic access.

Purpose of the Study:

  • To develop novel, triggerable polymeric nanoparticles for enhanced RNA delivery.
  • To create a diverse library of nanoparticles with light-responsive properties.
  • To evaluate the efficacy of these nanoparticles in gene knockdown and wound healing models.

Main Methods:

  • Synthesized a library of 160 triggerable polymeric nanoparticle formulations.
  • Assessed nanoparticle physico-chemical properties and light responsiveness.
  • Evaluated gene-knockdown efficiency compared to commercial lipofectamine.
  • Investigated cellular internalization and endosomal escape kinetics.
  • Tested efficacy in an acute skin wound healing model using miRNA-150-5p.

Main Results:

  • Identified six nanoparticle formulations with superior gene-knockdown activity (up to 500% increase).
  • Demonstrated differential cellular internalization and rapid endosomal escape (minutes).
  • Confirmed effective release of small interfering RNA (siRNA) and microRNA (miRNA).
  • Showed accelerated skin wound healing in vivo when treated with miRNA-150-5p loaded nanoparticles.

Conclusions:

  • Light-activatable polymeric nanoparticles offer a promising new strategy for topical RNA delivery.
  • These nanoparticles overcome key barriers in cellular uptake and cytoplasmic delivery.
  • The developed system effectively delivers non-coding RNAs for therapeutic applications, including wound healing.