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

Steven T.G. Street, Yunxiang He, Xu Hui Jin, Lorna Hodgson, Paul Verkade, Ian Manners*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Polymer-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.

Original languageEnglish
Pages (from-to)8394-8408
Number of pages15
JournalChemical Science
Volume11
Issue number32
DOIs
Publication statusPublished - 28 Aug 2020

Bibliographical note

Publisher Copyright:
© The Royal Society of Chemistry.

ASJC Scopus subject areas

  • General Chemistry

Fingerprint

Dive into the research topics of 'Cellular uptake and targeting of low dispersity, dual emissive, segmented block copolymer nanofibers'. Together they form a unique fingerprint.

Cite this