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RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...

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Chitosan/Interfering RNA Nanoparticle Mediated Gene Silencing in Disease Vector Mosquito Larvae

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Chitosan-Based Nanoparticles for Twist1 Knockdown in 4T1 Cells.

Asim Mushtaq¹, Li Li², Anitha A¹

¹School of Chemistry and Molecular Biosciences, The University of Queensland, Cooper Road, Brisbane, Queensland, 4072, Australia.

Macromolecular Bioscience

|April 10, 2025

Summary

Targeted nanoparticles effectively deliver twist1-siRNA to combat bone metastatic breast cancer. These chitosan-based nanoparticles show promise in improving treatment outcomes for this aggressive cancer.

Keywords:

SiRNA delivery chitosan nanomedicine poly(ethylene glycol)twist1

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Preparation and Characterization of SDF-1α-Chitosan-Dextran Sulfate Nanoparticles

Preparation and Characterization of SDF-1α-Chitosan-Dextran Sulfate Nanoparticles

Published on: January 22, 2015

Area of Science:

Biomedical Engineering
Nanotechnology
Oncology

Background:

Bone metastatic breast cancer significantly impacts patient quality of life and survival.
Current treatments face limitations in effectively targeting metastatic sites.
RNA interference (RNAi) offers a potential therapeutic avenue, but efficient delivery is crucial.

Purpose of the Study:

To develop and evaluate chitosan-based nanoparticles (NPs) for targeted delivery of twist1-siRNA.
To compare the efficacy of actively targeted (ALD-PEG-CHI) and passively targeted (mPEG-CHI) NPs.
To assess the in vitro therapeutic potential of these NPs against bone-metastatic breast cancer cells.

Main Methods:

Fabrication of alendronate-conjugated PEG-functionalized chitosan (ALD-PEG-CHI) and PEG-functionalized chitosan (mPEG-CHI) nanoparticles.
Encapsulation of twist1-siRNA within the NPs and characterization of size, zeta potential, and serum stability.
In vitro assessment of NP-mediated twist1 knockdown in 4T1 breast cancer cells using protein expression analysis and wound healing assays.

Main Results:

Both ALD-PEG-CHI-siRNA and mPEG-CHI-siRNA NPs were successfully synthesized with sizes under 70 nm and near-neutral zeta potential.
Complete encapsulation of twist1-siRNA was confirmed, with NPs providing significant serum protection (6h for ALD-PEG-CHI, 4h for mPEG-CHI).
Demonstrated effective twist1 knockdown in 4T1 cells, inhibiting directional cell migration.

Conclusions:

Chitosan-based nanoparticles show potential as effective delivery systems for twist1-siRNA in treating bone-metastatic breast cancer.
Both active and passive targeting strategies utilizing these NPs are promising for therapeutic applications.
Further in vivo studies are warranted to validate the therapeutic efficacy of these nanocarriers.