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Ionic-crosslinked polysaccharide/PEI/DNA nanoparticles for stabilized gene delivery
Ying Zhang1, Lin Lin2, Liang Liu1
1Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China; University of Chinese Academy of Sciences, Beijing 100039, China.
Carbohydrate Polymers
|September 23, 2018
Summary
Calcium-crosslinked alginate-shielded PEI/DNA nanoparticles show improved stability and longer circulation for enhanced gene delivery and tumor treatment.
Area of Science:
- Biotechnology
- Nanomedicine
- Gene Therapy
Background:
- Gene therapy requires stable delivery systems for systemic circulation.
- Polyethyleneimine (PEI)/DNA complexes are common gene carriers but can lack stability.
- Polysaccharide shielding is explored to enhance gene delivery vehicle stability.
Purpose of the Study:
- To improve the stability and circulation time of PEI/DNA complexes for gene therapy.
- To develop a novel nanoparticle system using alginate shielding and calcium crosslinking.
- To evaluate the potential of these nanoparticles for tumor targeting and treatment.
Main Methods:
- Screening of four polysaccharides, with sodium alginate identified as optimal.
- Formation of Alg/PEI/DNA complexes and subsequent crosslinking with calcium ions (Ca2+) to create Ca2+/(Alg/PEI/DNA) nanoparticles.
- In vitro and in vivo stability assessments, pharmacokinetic studies, and evaluation of nanoparticle accumulation at tumor sites.
Main Results:
- Ca2+/(Alg/PEI/DNA) nanoparticles demonstrated significantly enhanced stability compared to PEI/DNA and Alg/PEI/DNA complexes.
- Pharmacokinetic studies revealed prolonged blood circulation time for the Ca2+/(Alg/PEI/DNA) nanoparticles.
- Improved nanoparticle accumulation at tumor sites was observed, likely due to the enhanced permeability and retention (EPR) effect.
Conclusions:
- Alginate shielding and calcium crosslinking create a robust nanoparticle platform for gene delivery.
- The enhanced stability and circulation of Ca2+/(Alg/PEI/DNA) nanoparticles are beneficial for tumor targeting.
- This nanoparticle system shows promise for improving gene therapy efficacy and cancer treatment outcomes.
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