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A tetrahedral framework DNA-based bioswitchable miR-26a-5p delivery system for idiopathic pulmonary fibrosis

Ziwei Lei1,2,3, Cheng Chen2,3, Jiajie Shi2,3

  • 1Department of Burn Surgery, The First Affiliated Hospital, Naval Medical University, Shanghai, 200433, China.

Materials Today. Bio
|June 15, 2026
PubMed

Insights

A novel nanodelivery system, BiRDS26, effectively delivers miR-26a-5p to combat idiopathic pulmonary fibrosis (IPF). This system shows significant anti-fibrotic activity by targeting key signaling pathways, offering new hope for IPF treatment.

Area of Science:

  • Biotechnology
  • Nanomedicine
  • Molecular Biology

Background:

  • Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease with limited treatment options.
  • MicroRNAs, particularly miR-26a-5p, show promise against fibrosis but face delivery challenges.
  • Enzymatic degradation and poor cellular uptake hinder miRNA clinical application.

Purpose of the Study:

  • To develop a novel bioswitchable miRNA delivery system for targeted miR-26a-5p delivery.
  • To evaluate the anti-fibrotic efficacy of the developed system in IPF models.
  • To elucidate the underlying molecular mechanisms of the anti-fibrotic effects.

Main Methods:

  • Development of a tetrahedral framework nucleic acid-based bioswitchable miRNA delivery system (BiRDS26).
  • In vitro and in vivo testing of BiRDS26 for anti-fibrotic activity in IPF models.
  • Analysis of Hippo and Wnt signaling pathway modulation.

Main Results:

  • BiRDS26 successfully delivered miR-26a-5p, demonstrating potent anti-fibrotic effects.
  • The system showed efficacy in both in vitro and in vivo IPF models.
  • Coordinated suppression of Hippo and Wnt signaling pathways was observed.

Conclusions:

  • BiRDS26 is a rationally engineered nanotherapeutic platform for IPF treatment.
  • The system overcomes current limitations in miRNA delivery for fibrotic diseases.
  • BiRDS26 holds significant translational potential for managing idiopathic pulmonary fibrosis.
Keywords:
Bioswitchable miRNA delivery systemEMTGene deliveryLung fibrosisTetrahedral framework nucleic acidsmiRNA

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