Dual-reactive single-chain polymer nanoparticles for orthogonal functionalization through active ester and click chemistry.

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  • Additional Information
    • Source:
      Publisher: Elsevier Science Publishers Country of Publication: Netherlands NLM ID: 8607908 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-4995 (Electronic) Linking ISSN: 01683659 NLM ISO Abbreviation: J Control Release Subsets: MEDLINE
    • Publication Information:
      Original Publication: Amsterdam : Elsevier Science Publishers, 1984-
    • Subject Terms:
      Click Chemistry* ; Nanoparticles*/chemistry ; Esters*/chemistry ; Polymers*/chemistry ; Alkynes*/chemistry; Humans ; Glucose/chemistry ; Azides/chemistry ; Cycloaddition Reaction ; Copper/chemistry ; HeLa Cells
    • Abstract:
      Glucose has been extensively studied as a targeting ligand on nanoparticles for biomedical nanoparticles. A promising nanocarrier platform are single-chain polymer nanoparticles (SCNPs). SCNPs are well-defined 5-20 nm semi-flexible nano-objects, formed by intramolecularly crosslinked linear polymers. Functionality can be incorporated by introducing labile pentafluorophenyl (PFP) esters in the polymer backbone, which can be readily substituted by functional amine-ligands. However, not all ligands are compatible with PFP-chemistry, requiring different ligation strategies for increasing versatility of surface functionalization. Here, we combine active PFP-ester chemistry with copper(I)-catalyzed azide alkyne cycloaddition (CuAAC) click chemistry to yield dual-reactive SCNPs. First, the SCNPs are functionalized with increasing amounts of 1-amino-3-butyne groups through PFP-chemistry, leading to a range of butyne-SCNPs with increasing terminal alkyne-density. Subsequently, 3-azido-propylglucose is conjugated through the glucose C1- or C6-position by CuAAC click chemistry, yielding two sets of glyco-SCNPs. Cellular uptake is evaluated in HeLa cancer cells, revealing increased uptake upon higher glucose-surface density, with no apparent positional dependance. The general conjugation strategy proposed here can be readily extended to incorporate a wide variety of functional molecules to create vast libraries of multifunctional SCNPs.
      Competing Interests: Declaration of competing interest The authors declare no competing financial interest.
      (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
    • Contributed Indexing:
      Keywords: Active ester; Click chemistry; Controlled radical polymerization; Glucose; Single chain polymer nanoparticles; Surface functionalization; Thiol-Michael addition
    • Accession Number:
      0 (Esters)
      0 (Polymers)
      0 (Alkynes)
      IY9XDZ35W2 (Glucose)
      0 (Azides)
      789U1901C5 (Copper)
    • Publication Date:
      Date Created: 20240705 Date Completed: 20240909 Latest Revision: 20240910
    • Publication Date:
      20240911
    • Accession Number:
      10.1016/j.jconrel.2024.07.003
    • Accession Number:
      38968970