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Updated: Jul 21, 2025
Evaluation of Polymeric Gene Delivery Nanoparticles by Nanoparticle Tracking Analysis and High-throughput Flow Cytometry
Published on: March 1, 2013
pH-responsive polyzwitterion covered nanocarriers for DNA delivery
Xin Shen1, Anjaneyulu Dirisala2, Masahiro Toyoda1
1Laboratory for Chemistry and Life Science, Institute of Innovative Research, Tokyo Institute of Technology, 4259 Nagatsutacho, Midori-ku, Yokohama, Kanagawa 226-8503, Japan; Department of Life Science and Technology, School of Life Science and Technology, Tokyo Institute of Technology, 4259 Nagatsutacho, Midori-ku, Yokohama, Kanagawa 226-8503, Japan.
This study introduces a novel pH-responsive polyplex micelle for gene therapy. This nanocarrier enhances cellular uptake and endosomal escape, improving gene delivery and tumor growth suppression.
Area of Science:
- Biotechnology
- Nanomedicine
- Gene Therapy
Background:
- Gene therapy requires effective in vivo gene nanocarriers.
- Poly(ethylene glycol) (PEG)ylation improves circulation but reduces cellular uptake and transfection efficiency.
- Overcoming PEGylation's limitations is crucial for successful gene delivery.
Purpose of the Study:
- To develop a pH-responsive polyplex micelle for enhanced plasmid DNA delivery.
- To improve cellular uptake and endosomal escape for efficient gene transfection.
- To achieve effective tumor growth suppression via gene delivery.
Main Methods:
- Development of a stepwise pH-responsive polyplex micelle.
- Surface modification with ethylenediamine-based polycarboxybetaines.
- Evaluation of charge switching, blood circulation, tumor accumulation, and gene transfection efficiency.
Main Results:
- The polyplex micelle exhibited a pH-dependent charge switch from neutral to positive at tumor and endo-/lysosomal pH.
- Enhanced cellular uptake and facilitated endosomal escape were observed.
- Prolonged blood circulation, increased tumor accumulation, and significant tumor growth suppression were achieved using an antiangiogenic gene.
Conclusions:
- pH-responsive, charge-switchable polyplex micelles are effective for nucleic acid delivery.
- This strategy overcomes PEGylation-induced limitations in gene therapy.
- The developed nanocarrier shows promise for efficient in vivo gene therapy and cancer treatment.
