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Assembly and Characterization of Polyelectrolyte Complex Micelles
Published on: March 2, 2020
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Polycation Architecture Affects Complexation and Delivery of Short Antisense Oligonucleotides: Micelleplexes
Christian J Grimme1, Mckenna G Hanson2, Louis G Corcoran2
1Department of Chemical Engineering & Materials Science, University of Minnesota, 421 Washington Avenue SE, Minneapolis, Minnesota 55455, United States.
Biomacromolecules
|July 21, 2022
Summary
Cationic micelles serve as superior delivery vehicles for antisense oligonucleotides (ASOs). Vehicle architecture significantly impacts biological performance, with specific micelleplexes showing enhanced gene silencing and stability for ASO delivery.
Area of Science:
- Polymer chemistry and nanomedicine
- Oligonucleotide delivery systems
- Biomaterials for gene therapy
Background:
- Antisense oligonucleotides (ASOs) require effective delivery vehicles for therapeutic applications.
- Polymer-based nanoparticles offer potential for complexing and delivering nucleic acids.
- Understanding the impact of polymer architecture on delivery efficiency is crucial.
Purpose of the Study:
- To evaluate four polymer derivatives forming polyplexes and micelleplexes for antisense oligonucleotide (ASO) complexation and biological delivery.
- To compare the performance of different polymer architectures in terms of ASO loading, stability, cellular uptake, gene silencing, and toxicity.
- To determine the optimal vehicle architecture for efficient and safe ASO delivery.
Main Methods:
- Synthesis and characterization of four polymer derivatives: poly(2-dimethylaminoethyl methacrylate) (D), poly(ethylene glycol)methylether methacrylate-block-poly(2-dimethylaminoethyl methacrylate) (ObD), poly(2-dimethylaminoethyl methacrylate)-block-poly(n-butyl methacrylate) (DB), and poly(ethylene glycol)methylether methacrylate-block-poly(2-dimethylaminoethyl methacrylate)-block-poly(n-butyl methacrylate) (ObDB).
- Complexation of ASOs with polymer derivatives to form polyplexes and micelleplexes.
- Assessment of colloidal stability, ASO loading, cellular uptake, gene silencing efficacy, and in vitro toxicity of the developed delivery systems.
Main Results:
- Both polyplexes and micelleplexes successfully complexed ASOs, with Ob brush incorporation enhancing colloidal stability.
- Micelleplex formation was independent of formulation order, ensuring ease, versatility, and reproducibility.
- DB micelleplexes exhibited the highest gene silencing, cellular internalization, and tolerable toxicity.
- ObDB micelleplexes demonstrated superior colloidal stability and payload trafficking, despite lower cellular uptake.
Conclusions:
- Cationic micelles represent superior delivery vehicles for ASOs compared to other architectures.
- The architectural design of the polymer vehicle is a critical determinant of biological performance for ASO delivery.
- This study highlights the potential of tailored polymer micelles for effective and safe oligonucleotide-based therapeutics.
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