Optimization of precision nanofiber micelleplexes for DNA delivery

Steven T.G. Street, Hayley C. Parkin, Lennard Shopperly, Josie Chrenek, Keiran Letwin, Stephanie M. Willerth*, Ian Manners*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

6 Citations (Scopus)

Abstract

As nucleic acid (NA) technologies continue to revolutionize medicine, new delivery vehicles are needed to effectively transport NA cargoes into cells. Uniform and length-tunable nanofiber micelleplexes have recently shown promise as versatile polymeric delivery vehicles for plasmid DNA, however the effects of several key parameters on micelleplex transfection and stability remain unknown. In this work, we compare poly(fluorenetrimethylenecarbonate)-b-poly(2-(dimethylamino)ethyl methacrylate) (PFTMC-b-PDMAEMA) nanofiber micelleplexes to nanosphere micelleplexes and PDMAEMA polyplexes, examining the effects of complexation buffer, the temporal and serum stability of nanofiber micelleplexes, as well as the effects of cell density, cell type, and polymer DPn upon transfection efficiency and cell viability. These studies are vital for understanding the formation and biological activity of micelleplexes in more detail and should inform the future design of more advanced polymeric NA delivery systems.

Original languageEnglish
Number of pages12
JournalBiomaterials Science
Volume11
Issue number10
Early online date8 Mar 2023
DOIs
Publication statusE-pub ahead of print - 8 Mar 2023

Bibliographical note

Funding Information:
S. T. G. Street thanks NSERC (Canada) for funding and the EPSRC (UK) for a DTP Doctoral Prize Fellowship (EP/N509619/1). H. C. Parkin thanks UVic for a graduate award for chemistry excellence (GRACE) and NSERC (Canada) for funding. L. Shopperly, J. Chrenek, K. Letwin and S. Willerth thank NSERC (Canada) and the latter for a Canadian Government for a Canada Research Chair. I. Manners thanks NSERC (Canada) for an NSERC Discovery Grant, the Canadian Government for a Canada 150 Research Chair, the University of Victoria for start-up funds and the Canada Foundation for Innovation (CFI), and the British Columbia Knowledge Development Fund (BCKDF) for equipment and instrumentational support. The authors wish to gratefully acknowledge the CAMTEC biomedical core for use of cell culture facilities, as well as the UVic Electron Microscopy Laboratory for the use of TEM facilities and Rebecca Hof for assistance with plasmid amplification. The HEK293 cells (human female embryonic kidney cells) were purchased from the American Type Culture Collection (ATCC) through Cedarlane Corporation (Canada).

Publisher Copyright:
© 2023 The Royal Society of Chemistry.

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