Related Experiment Video
Updated: Mar 14, 2026
Preparation of Neutrally-charged, pH-responsive Polymeric Nanoparticles for Cytosolic siRNA Delivery
Published on: May 2, 2019
Comparing Gene Silencing and Physiochemical Properties in siRNA Bound Cationic Star-Polymer Complexes
Megan Dearnley1, Nicholas P Reynolds2, Peter Cass3
1CSIRO-Health and Biosecurity Business Unit, Australian Animal Health Laboratory , 5 Portarlington Road, Geelong, Vic 3220, Australia.
Abstract:
The translation of siRNA into clinical therapies has been significantly delayed by issues surrounding the delivery of naked siRNA to target cells. Here we investigate siRNA delivery by cationic acrylic polymers developed by Reversible Addition-Fragmentation chain Transfer (RAFT) mediated free radical polymerization. We investigated cell uptake and gene silencing of a series of siRNA-star polymer complexes both in the presence and absence of a protein "corona". Using a multidisciplinary approach including quantitative nanoscale mechanical-atomic force microscopy, dynamic light scattering and nanoparticle tracking analysis we have characterized the nanoscale morphology, stiffness, and surface charge of the complexes with and without the protein corona. This is one of the first examples of a comprehensive physiochemical analysis of siRNA-polymer complexes being performed alongside in vitro biological assays, allowing us to describe a set of desirable physical features of cationic polymer complexes that promote gene silencing. Multifaceted studies such as this will improve our understanding of structure-function relationships in nanotherapeutics, facilitating the rational design of polymer-mediated siRNA delivery systems for novel treatment strategies.
Insights
Cationic acrylic polymers effectively deliver small interfering RNA (siRNA) for gene silencing. This study characterizes polymer-siRNA complexes, identifying key physical properties for successful therapeutic delivery.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Molecular Biology
Background:
- Clinical translation of small interfering RNA (siRNA) therapies is hindered by delivery challenges.
- Naked siRNA faces difficulties in reaching target cells effectively.
Purpose of the Study:
- To investigate siRNA delivery using cationic acrylic polymers synthesized via Reversible Addition-Fragmentation chain Transfer (RAFT) polymerization.
- To analyze the impact of protein corona on siRNA-polymer complex characteristics and biological activity.
- To establish structure-function relationships for optimized nanotherapeutic design.
Main Methods:
- Synthesis of siRNA-star polymer complexes using RAFT polymerization.
- Characterization using nanoscale mechanical-atomic force microscopy, dynamic light scattering, and nanoparticle tracking analysis.
- In vitro assessment of cell uptake and gene silencing efficacy.
Main Results:
- Comprehensive physiochemical analysis of siRNA-polymer complexes, with and without protein corona.
- Identification of desirable physical features (morphology, stiffness, surface charge) promoting gene silencing.
- Correlation between physical properties and biological performance of the nanodelivery system.
Conclusions:
- Cationic acrylic polymers show promise for effective siRNA delivery.
- Understanding physiochemical properties is crucial for designing efficient polymer-mediated siRNA nanotherapeutics.
- This multidisciplinary approach facilitates rational design for novel therapeutic strategies.
Related Concept Videos
02:30siRNA - Small Interfering RNAs
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the...
01:24Site-Targeted Drug Delivery Systems: Polymeric Carriers