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Core-Shell Structured Chitosan-Polyethylenimine Nanoparticles for Gene Delivery: Improved Stability, Cellular Uptake,
Jens Casper1, Laura Nicolle2, Melanie Willimann3
1Division of Pharmaceutical Technology, Department of Pharmaceutical Sciences, University of Basel, Basel, CH-4056, Switzerland.
Macromolecular Bioscience
|October 6, 2022
Summary
Researchers developed novel core-shell nanoparticles using functionalized chitosan for improved nucleic acid delivery. These advanced gene delivery systems show enhanced cellular uptake and potent transfection in vitro and in vivo.
Area of Science:
- Biotechnology and Biomedical Engineering
- Gene Therapy and Delivery Systems
Background:
- Nonviral gene delivery systems are crucial for nucleic acid delivery but face challenges with low transgene expression and limited tolerability.
- Depolymerized chitosan-polyethylenimine DNA complexes (dCS-PEI/DNA) offer potential for improved gene delivery vectors.
Purpose of the Study:
- To investigate the enhancement of nucleic acid delivery using depolymerized chitosan-polyethylenimine DNA complexes (dCS-PEI/DNA).
- To evaluate the impact of functional shell components, including polyethylene glycol (PEG) and cell-penetrating peptides, on physicochemical and biological properties of gene delivery nanoparticles.
- To optimize ternary core-shell structured nanoparticles for improved gene delivery efficiency.
Main Methods:
- Development of core-shell nanoparticles with a dCS-PEI/DNA core and a dCS-PEG-COOH shell.
- Functionalization of nanoparticles with polyethylene glycol (PEG) and cell-penetrating peptides.
- Evaluation of physicochemical characteristics, cellular uptake, and transfection potency in human hepatoma HuH-7 cells and murine primary hepatocytes.
- In vivo assessment of transgene expression in wild-type mice following retrograde intrabiliary infusion.
Main Results:
- The optimized ternary complex, combining a dCS-linear PEI/DNA core with a dCS-PEG-COOH shell, demonstrated enhanced nucleic acid encapsulation, cellular uptake, and transfection potency.
- In vitro transfection potency was confirmed in human hepatoma HuH-7 cells and murine primary hepatocytes.
- In vivo studies in wild-type mice showed high reporter gene expression for three days after administration of only 100 ng complexed DNA via retrograde intrabiliary infusion.
Conclusions:
- Functionalized chitosan-based ternary core-shell nanoparticles represent a promising platform for efficient in vitro and in vivo gene delivery.
- The modular design allows for systematic evaluation and optimization of nanoparticle components for enhanced gene delivery performance.
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