Cellular uptake and targeting of low dispersity, dual emissive, segmented block copolymer nanofibers

dc.contributor.authorStreet, Steven T. G.
dc.contributor.authorHe, Yunxiang
dc.contributor.authorJin, Xu-Hui
dc.contributor.authorHodgson, Lorna
dc.contributor.authorVerkade, Paul
dc.contributor.authorManners, Ian
dc.description.abstractPolymer-based nanoparticles show substantial promise in the treatment and diagnosis of cancer and other diseases. Herein we report an exploration of the cellular uptake of tailored, low dispersity segmented 1D nanoparticles which were prepared from an amphiphilic block copolymer, poly(dihexylfluorene)-b-poly(ethyleneglycol) (PDHF13-b-PEG227), with a crystallizable PDHF core-forming block and a ‘stealth’ PEG corona-forming block with different end-group functionalities. Segmented C–B–A–B–C pentablock 1D nanofibers with varied spatially-defined coronal chemistries and a selected length (95 nm) were prepared using the living crystallization-driven self-assembly (CDSA) seeded-growth method. As the blue fluorescence of PDHF is often subject to environment-related quenching, a far-red BODIPY (BD) fluorophore was attached to the PEG end-group of the coronal B segments to provide additional tracking capability. Folic acid (FA) was also incorporated as a targeting group in the terminal C segments. These dual-emissive pentablock nanofibers exhibited uptake into >97% of folate receptor positive HeLa cells by flow cytometry. In the absence of FA, no significant uptake was detected and nanofibers with either FA or BD coronal groups showed no significant toxicity. Correlative light and electron microscopy (CLEM) studies revealed receptor-mediated endocytosis as an uptake pathway, with subsequent localization to the perinuclear region. A significant proportion of the nanofibers also appeared to interact with the cell membrane in an end-on fashion, which was coupled with fluorescence quenching of the PDHF core. These results provide new insights into the cellular uptake of polymer-based nanofibers and suggest their potential use in targeted therapies and diagnostics.en_US
dc.description.sponsorshipS. Street thanks the EPSRC (UK) for a DTP Doctoral Prize Fellowship (EP/N509619/1). I. Manners thanks NSERC (Canada) for an NSERC Discovery Grant, the Canadian Government for a Canada 150 Research Chair, the University of Victoria for startup funds and the Canada Foundation for Innovation (CFI), and the British Columbia Knowledge Development Fund (BCKDF) for equipment and instrumentational support. Y. He thanks the EPSRC funded Bristol Chemical Synthesis CDT for funding. L. Hodgson thanks the BBSRC (UK) for a strategic LoLa award (BB/ M002969/1). The authors wish to acknowledge the assistance of Dr Andrew Herman and Lorena Sueiro Ballesteros and the University of Bristol Faculty of Biomedical Sciences Flow Cytometry Facility with ow cytometry experiments, BrisSynBio (BB/L01386X/1) for use of cell culture facilities, and Prof. Cornelia Bohne for use of the QM40 uorimeter. S. Street and Y. He also thank the Bristol Chemistry Electron Microscopy Unit for the use of TEM facilities. All the authors would like to thank Jon Lane for providing the GRASP65-GFP HeLa cell line, Prof. M. C. Galan for providing WI-38 cells, and Holly Baum, George Banting, and Dek Woolfson for useful discussions (supported by BBSRC grants BB/L010518/1 and BB/L01386X/1). We are grateful for the support by the EM and LM units of the Wolfson Bioimaging Facility (BBSRC grant BB/L014181/1). The authors also wish to thank the reviewers for their insightful comments and suggestions.en_US
dc.identifier.citationHe, Y., Hodgson, L., Jin, X., Manners, I., Street, S. T. G., & Verkade, P. (2020). Cellular uptake and targeting of low dispersity, dual emissive, segmented block copolymer nanofibers. Chemical Science, 11(32), 8394-8408. https://doi.org/10.1039/d0sc02593cen_US
dc.publisherChemical Scienceen_US
dc.titleCellular uptake and targeting of low dispersity, dual emissive, segmented block copolymer nanofibersen_US


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