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Updated: Jun 4, 2025

Preparation of Neutrally-charged, pH-responsive Polymeric Nanoparticles for Cytosolic siRNA Delivery

Preparation of Neutrally-charged, pH-responsive Polymeric Nanoparticles for Cytosolic siRNA Delivery

Published on: May 2, 2019

Polymer-siRNA nanovectors for treating lung inflammation.

Ritabrita Goswami¹, Harini Nagaraj¹, Yagiz Anil Cicek¹

¹Department of Chemistry, University of Massachusetts Amherst, 710 North Pleasant Street, Amherst, MA 01003, USA.

Journal of Controlled Release : Official Journal of the Controlled Release Society

|December 27, 2024

Summary

This summary is machine-generated.

New guanidinium-functionalized polymers (Cn-Guan) effectively deliver small interfering RNA (siRNA) for lung inflammation treatment. These polymers show promise for developing safer and more efficient therapies for pulmonary diseases.

Keywords:

Anti-inflammatory Lung inflammation Polymers Polyplex siRNA

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Synthesis, Functionalization, and Characterization of Fusogenic Porous Silicon Nanoparticles for Oligonucleotide Delivery

Published on: April 16, 2019

Area of Science:

Biomaterials Science
Nanotechnology
Pulmonary Medicine

Background:

Uncontrolled lung inflammation drives many diseases, with current treatments causing side effects.
Small interfering RNA (siRNA) offers therapeutic immune regulation but faces delivery challenges like cellular uptake and tissue localization.

Purpose of the Study:

To investigate guanidinium-functionalized polymers (Cn-Guan) for optimizing siRNA delivery and efficacy in treating lung inflammation.
To explore the impact of polymer amphiphilicity, side chain length, and molecular weight on siRNA complexation and therapeutic outcomes.

Main Methods:

Synthesized nine Cn-Guan polymers with varying side chain lengths (C3, C5, C7) and molecular weights (17, 30, 65 kDa).
Formed polyplexes with siRNA and characterized their size and complexation efficiency.
Evaluated in vitro gene knockdown and in vivo lung accumulation and inflammation reduction in a murine model.

Main Results:

C7-Guan/siRNA polyplexes showed the smallest size and tightest siRNA complexation.
In vitro, 65 kDa polymers yielded highest knockdown; C3/C5-Guan/siRNA achieved ~70% knockdown.
In vivo, C7-Guan/siRNA demonstrated superior lung accumulation and ~70% TNF-α knockdown at a low dose, suggesting enhanced serum stability.

Conclusions:

Cn-Guan/siRNA polyplexes are effective and safe for attenuating pulmonary inflammation.
Polymer properties significantly influence siRNA delivery and therapeutic efficacy.
These findings provide insights for developing advanced siRNA delivery vectors for lung diseases.