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Evaluation of Polymeric Gene Delivery Nanoparticles by Nanoparticle Tracking Analysis and High-throughput Flow Cytometry

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Published on: March 1, 2013

Polymeric Gene Delivery at Sub-Stoichiometric N/P Ratios.

Yi Wu¹, Xuejing Cheng¹, Yuanchi Wang¹

¹Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, 200241, China.

Polymer Science & Technology (Washington, D.C.)

|June 8, 2026

Summary

A novel fluorinated polymer enables potent gene delivery at low nitrogen-to-phosphorus (N/P) ratios, overcoming the efficiency-toxicity trade-off. This breakthrough offers a safer and more effective approach for nucleic acid therapeutics.

Keywords:

endosomal escape fluorination gene transfection low nitrogen-to-phosphorus ratios polymer

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Area of Science:

Biomaterials Science
Gene Therapy
Polymer Chemistry

Background:

Efficient cytosolic delivery of nucleic acid therapeutics is crucial for clinical applications.
Cationic polymers are effective gene carriers but face a trade-off between transfection efficiency and cytotoxicity due to high N/P ratios.

Purpose of the Study:

To develop a novel gene delivery vector that achieves high transfection efficiency at low N/P ratios.
To investigate the mechanism of gene delivery and intracellular trafficking of the novel vector.

Main Methods:

Synthesis and characterization of a novel fluorinated polymer.
DNA condensation and polyplex formation studies at varying N/P ratios.
Cellular uptake, intracellular trafficking, and transfection efficiency assays in diverse cell lines.

Main Results:

The fluorinated polymer efficiently condensed DNA into stable nanoparticles at N/P ratios below 1, with negligible free polymer.
Scavenger-receptor-mediated endocytosis, rapid endosomal escape, and nuclear entry were observed within 4 hours.
Broad applicability was demonstrated across various cell lines with successful delivery of protein-expressing plasmids.

Conclusions:

The fluorinated polymer represents a new class of highly efficient gene vectors with minimal cytotoxicity.
This study provides a rational design strategy for next-generation gene delivery systems.
The findings pave the way for improved nucleic acid therapeutics with enhanced safety and efficacy.