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

Autor: Paats JD; Department of Molecules and Materials, MESA+ Institute for Nanotechnology and TechMed Institute for Health and Biomedical Technologies, Faculty of Science and Technology, University of Twente, P.O. Box 217, 7500, AE, Enschede, the Netherlands., Hamelmann NM; Department of Molecules and Materials, MESA+ Institute for Nanotechnology and TechMed Institute for Health and Biomedical Technologies, Faculty of Science and Technology, University of Twente, P.O. Box 217, 7500, AE, Enschede, the Netherlands., Paulusse JMJ; Department of Molecules and Materials, MESA+ Institute for Nanotechnology and TechMed Institute for Health and Biomedical Technologies, Faculty of Science and Technology, University of Twente, P.O. Box 217, 7500, AE, Enschede, the Netherlands. Electronic address: j.m.j.paulusse@utwente.nl.
Jazyk: angličtina
Zdroj: Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2024 Sep; Vol. 373, pp. 117-127. Date of Electronic Publication: 2024 Jul 14.
DOI: 10.1016/j.jconrel.2024.07.003
Abstrakt: 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.)
Databáze: MEDLINE
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