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Gene-therapy Inspired Polycation Coating for Protection of DNA Origami Nanostructures
Published on: January 19, 2019
Folate mediated in vitro targeting of depolymerised trimethylated chitosan having arginine functionality.
Viola B Morris1, Chandra P Sharma
1Division of Biosurface Technology, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Science and Technology, Poojappura, Thiruvananthapuram 695 012, Kerala, India.
Journal of Colloid and Interface Science
|June 29, 2010
Summary
Researchers developed a novel polymer nanoparticle for cancer gene therapy. This folate-mediated delivery system enhances cell uptake and nuclear DNA delivery, showing promise for targeted cancer treatments.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Gene Therapy
Background:
- Targeted delivery vectors are crucial for effective cancer gene therapy.
- Folate receptor-mediated targeting offers a promising strategy for cancer cell-specific delivery.
Purpose of the Study:
- To synthesize and characterize a novel folate-conjugated polymer nanoparticle (ATFP15H) for enhanced gene delivery.
- To evaluate the DNA protection, blood compatibility, cellular uptake, and transfection efficiency of the ATFP15H nanoparticles.
Main Methods:
- Conjugation of poly(ethylene glycol)-folate (PEG-FA) with arginine modified chitosan (ATFP15H).
- Formation of core-shell nanostructures with plasmid DNA.
- Assessment of DNA protection, buffering capacity, blood compatibility (hemolysis, aggregation, platelet activation), cell viability, and transfection efficiency in KB cells.
- Flow cytometry and YOYO labeling for cellular uptake and nuclear localization studies.
Main Results:
- ATFP15H nanoparticles demonstrated good buffering capacity and protected DNA from degradation and plasma protein interference.
- The nanoparticles exhibited excellent blood compatibility.
- Enhanced cell growth was observed at 10 microg concentration.
- Transfection efficiency was comparable to PEI in folate receptor-positive KB cells.
- Superior colloidal stability led to increased cellular uptake and nuclear localization compared to unmodified chitosan.
Conclusions:
- The developed ATFP15H nanoparticle is a safe and effective vector for folate-mediated cancer gene therapy.
- Its enhanced cellular uptake and nuclear delivery highlight its potential for targeted cancer treatment applications.
