Surface engineering of metal-organic framework nanoparticles-based miRNA carrier: Boosting RNA stability, intracellular delivery and synergistic therapy

Weiguang Jin, Xin Li, Sergio Mercado Argandona, Roslyn M. Ray, Marie Karen Tracy Hong Lin, Francesca Melle, Gael Clergeaud, Thomas Lars Andresen, Martin Nielsen, David Fairen‐Jimenez, Kira Astakhova*, Katrine Qvortrup

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

MicroRNAs (miRNAs) are small noncoding RNAs that are critical for the regulation of multiple physiological and pathological processes, thus holding great clinical potential. However, the therapeutic applications of miRNAs are severely limited by their biological instability and poor intracellular delivery. Herein, we describe a dual-layers surface engineering strategy to design an efficient miRNA delivery nanosystem based on metal–organic frameworks (MOFs) incorporating lipid coating. The resulting nanoparticle system was demonstrated to protect miRNA from ribonuclease degradation, enhance cellular uptake and facilitate lysosomal escape. These ensured effective miRNA mediated gene therapy, which synergized with MOF-specific photodynamic therapy and pre-encapsulated doxorubicin (Dox) chemotherapy to provide a multifunctional with therapeutic effectiveness against cencer cells The mechanisms of miRNA binding and Dox loading were revealed, demonstrating the potential of the present MOFs surface-engineered strategy to overcome their inherent pore-size restriction for macromolecular miRNA carrying, enableefficient co-delivery. In vitro studies revealed the potential of our multifunctional system for miRNA delivery and the demonstrated the therapeutic effectiveness against cancer cells, thereby providing a versatile all-in-one MOFs strategy for delivery of nucleic acids and diverse therapeutic molecules in synergistic therapy.

Original languageEnglish
JournalJournal of Colloid and Interface Science
Volume677
Pages (from-to)429-440
ISSN0021-9797
DOIs
Publication statusPublished - 2025

Keywords

  • Co-carrying
  • Intracellular delivery
  • Metal–organic frameworks
  • miRNA stabilization
  • Surface engineering
  • Synergistic treatment

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