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Related Experiment Video

Updated: Aug 9, 2025

Preparation of Neutrally-charged, pH-responsive Polymeric Nanoparticles for Cytosolic siRNA Delivery
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Engineered Polymer-siRNA Polyplexes Provide Effective Treatment of Lung Inflammation.

Taewon Jeon1,2, David C Luther2, Ritabrita Goswami2

  • 1Molecular and Cellular Biology Graduate Program, University of Massachusetts Amherst, 230 Stockbridge Road, Amherst, Massachusetts 01003, USA.

ACS Nano
|February 21, 2023
PubMed
Summary

Engineered polymers effectively deliver small interfering RNA (siRNA) to lung tissue, overcoming cellular barriers to treat inflammation. This novel approach shows significant gene silencing in vitro and in vivo for respiratory diseases.

Keywords:
Anti-inflammatorycytosolic deliverylung inflammationpolymerpolyplexsiRNA

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Area of Science:

  • Biotechnology
  • Nanomedicine
  • Pulmonary Medicine

Background:

  • Uncontrolled lung inflammation drives acute and chronic respiratory diseases.
  • Small interfering RNA (siRNA) offers therapeutic potential but faces delivery challenges like endosomal entrapment and poor lung targeting.
  • Developing effective delivery systems is crucial for siRNA-based pulmonary treatments.

Purpose of the Study:

  • To develop and evaluate an engineered cationic polymer (PONI-Guan) for efficient siRNA delivery to lung tissue.
  • To assess the in vitro and in vivo anti-inflammatory efficacy of PONI-Guan/siRNA polyplexes.
  • To demonstrate targeted delivery and gene silencing in inflamed pulmonary tissue.

Main Methods:

  • Synthesis of an engineered cationic polymer, PONI-Guan.
  • Formation of polyplexes with small interfering RNA (siRNA).
  • In vitro assessment of gene knockdown efficiency.
  • In vivo administration of polyplexes in lipopolysaccharide (LPS)-challenged mice to evaluate lung targeting and TNF-α silencing.

Main Results:

  • PONI-Guan/siRNA polyplexes demonstrated efficient siRNA delivery to the cytosol, achieving >70% gene knockdown in vitro.
  • Polyplexes exhibited inherent targeting to inflamed lung tissue after intravenous administration.
  • A low siRNA dosage (0.28 mg/kg) resulted in >80% silencing of TNF-α expression in vivo.

Conclusions:

  • PONI-Guan is an effective carrier for siRNA delivery, overcoming cellular and organismal barriers for pulmonary applications.
  • The PONI-Guan/siRNA system shows significant potential for treating inflammatory lung diseases.
  • This strategy offers a promising low-dose, targeted approach for siRNA-based respiratory therapeutics.