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Synthesis of Stimuli-responsive Nanogels using Aqueous One-step Crosslinking and Co-nanopolymerization

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Decationized crosslinked polyplexes for redox-triggered gene delivery.

Luís Novo¹, Ethlinn V B van Gaal, Enrico Mastrobattista

¹Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The Netherlands.

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

|April 16, 2013

Summary

Neutral polymers offer safer gene delivery by reducing cytotoxicity. This study presents a novel neutral polymer system that efficiently condenses and protects plasmid DNA (pDNA), showing reduced toxicity and improved cellular uptake for enhanced gene therapy applications.

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Methionine Functionalized Biocompatible Block Copolymers for Targeted Plasmid DNA Delivery

Methionine Functionalized Biocompatible Block Copolymers for Targeted Plasmid DNA Delivery

Published on: August 6, 2019

Area of Science:

Biomaterials Science
Gene Therapy
Polymer Chemistry

Background:

Cationic polymers are widely used for gene delivery but exhibit significant cytotoxicity.
Developing neutral, biocompatible polymers that maintain DNA condensation and protection is crucial for safer gene therapy.

Purpose of the Study:

To introduce a novel, neutral polymeric gene delivery system.
To overcome the limitations of toxicity and instability associated with cationic gene delivery vectors.

Main Methods:

A three-step process involving charge-driven condensation, disulfide crosslinking, and polyplex decationization was employed.
Poly(hydroxypropyl methacrylamide) (pHPMA) was used to create a disulfide crosslinked core entrapping plasmid DNA (pDNA), with a poly(ethylene glycol) (PEG) shell.
The efficacy and safety of the resulting nanoparticles were evaluated in HeLa cells.

Main Results:

The developed neutral polyplexes demonstrated high and stable DNA loading capacity.
These polyplexes exhibited stealth behavior, reduced toxicity, and no interference with cell viability or metabolic activity.
Successful pDNA release and high reporter gene expression were observed after cellular uptake via disulfide bond cleavage in the reducing intracellular environment.

Conclusions:

The stabilized, decationized polyplexes offer a promising solution to the toxicity, stability, and specificity issues of cationic polymer-based gene delivery systems.
This neutral polymer approach enhances safety and efficacy, paving the way for advanced targeted gene therapy applications.