Modular Synthesis of Semiconducting Graft Copolymers to Achieve “Clickable” Fluorescent Nanoparticles with Long Circulation and Specific Cancer Targeting

Adam Creamer, Alessandra Lo Fiego, Alice Agliano, Lino Prados-Martin, Håkon Høgset, Adrian Najer, Daniel A. Richards, Jonathan P. Wojciechowski, James E.J. Foote, Nayoung Kim, Amy Monahan, Jiaqing Tang, André Shamsabadi, Léa N.C. Rochet, Ioanna A. Thanasi, Laura R. de la Ballina, Charlotte L. Rapley, Stephen Turnock, Elizabeth A. Love, Laurence BugeonMargaret J. Dallman, Martin Heeney, Gabriela Kramer-Marek, Vijay Chudasama, Federico Fenaroli, Molly M. Stevens*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Semiconducting polymer nanoparticles (SPNs) are explored for applications in cancer theranostics because of their high absorption coefficients, photostability, and biocompatibility. However, SPNs are susceptible to aggregation and protein fouling in physiological conditions, which can be detrimental for in vivo applications. Here, a method for achieving colloidally stable and low-fouling SPNs is described by grafting poly(ethylene glycol) (PEG) onto the backbone of the fluorescent semiconducting polymer, poly(9,9′-dioctylfluorene-5-fluoro-2,1,3-benzothiadiazole), in a simple one-step substitution reaction, postpolymerization. Further, by utilizing azide-functionalized PEG, anti-human epidermal growth factor receptor 2 (HER2) antibodies, antibody fragments, or affibodies are site-specifically “clicked” onto the SPN surface, which allows the functionalized SPNs to specifically target HER2-positive cancer cells. In vivo, the PEGylated SPNs are found to have excellent circulation efficiencies in zebrafish embryos for up to seven days postinjection. SPNs functionalized with affibodies are then shown to be able to target HER2 expressing cancer cells in a zebrafish xenograft model. The covalent PEGylated SPN system described herein shows great potential for cancer theranostics.

Original languageEnglish (US)
JournalAdvanced Materials
DOIs
StateAccepted/In press - 2023

Bibliographical note

Publisher Copyright:
© 2023 The Authors. Advanced Materials published by Wiley-VCH GmbH.

Keywords

  • fluorescent nanoparticles
  • graft copolymers
  • polymer brushes
  • polymer dots
  • semiconducting polymer nanoparticles

ASJC Scopus subject areas

  • General Materials Science
  • Mechanics of Materials
  • Mechanical Engineering

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