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Length-Controlled Nanofiber Micelleplexes as Efficient Nucleic Acid Delivery Vehicles
Steven T G Street1,2,3, Josie Chrenek4,5, Robert L Harniman1
1School of Chemistry, University of Bristol, Bristol BS8 1TS, U.K.
Journal of the American Chemical Society
|October 19, 2022
Summary
Short, 1D micelleplexes (polymeric nanoparticles) significantly enhance nucleic acid delivery for gene therapy. These precisely engineered nanofibers outperform spherical nanoparticles and traditional polyplexes in cellular transfection efficiency.
Area of Science:
- Polymer Science
- Nanotechnology
- Gene Delivery
Background:
- Micelleplexes are promising polymeric delivery systems for nucleic acids.
- Previous studies indicated spherical micelleplexes outperform polyplexes in cellular transfection.
- The impact of micelleplex morphology on transfection efficiency remained unexplored.
Purpose of the Study:
- To investigate the effect of micelleplex morphology on cellular transfection.
- To compare the properties and transfection activity of PFTMC-b-PDMAEMA nanofiber micelleplexes with nanosphere micelleplexes and polyplexes.
- To explore the influence of nanofiber length on transfection efficiency and cell viability.
Main Methods:
- Fabrication of precision, length-tunable PFTMC-b-PDMAEMA nanofiber micelleplexes.
- Characterization of DNA complexation using cryo-TEM, AFM, DLS, and ζ-potential measurements.
- Evaluation of transfection efficiency and cell viability in U-87 MG cells using a luciferase plasmid.
Main Results:
- Nanofiber micelleplexes were successfully prepared and characterized, showing distinct formation and properties compared to nanosphere micelleplexes and polyplexes.
- Short nanofiber micelleplexes (length < 100 nm) demonstrated superior cellular transfection efficiency.
- Short nanofiber micelleplexes outperformed nanosphere micelleplexes, polyplexes, longer nanofibers, and a commercial control (Lipofectamine 2000).
Conclusions:
- One-dimensional (1D) micelleplex morphology is crucial for optimizing nucleic acid delivery.
- Short nanofiber micelleplexes represent a highly effective platform for gene delivery applications.
- This research provides a foundation for developing advanced polymeric nucleic acid delivery vehicles.

