Glycosylated nanoparticles derived from RAFT polymerization for effective drug delivery to macrophages
File(s)
Author(s)
Type
Journal Article
Abstract
The functional group tolerance and simplicity of reversible addition fragmentation chain transfer (RAFT) polymerization enable its use in the preparation of a wide range of functional polymer architectures for a variety of applications, including drug delivery. Given the role of tumor-associated macrophages (TAMs) in cancer and their dependence on the tyrosine kinase receptor FMS (CSF-1R), the key aim of this work was to achieve effective delivery of an FMS inhibitor to cells using a polymer delivery system. Such a system has the potential to exploit biological features specific to macrophages and therefore provide enhanced selectivity. Building on our prior work, we have prepared RAFT polymers based on a poly(butyl methacrylate-co-methacrylic acid) diblock, which were extended with a hydrophilic block, a cross-linker, and a mannose-based monomer scaffold, exploiting the abundance of macrophage mannose receptors (MMRs, CD206) on the surface of macrophages. We demonstrate that the prepared polymers can be assembled into nanoparticles and are successfully internalized into macrophages, in part, via the MMR (CD206). Finally, we showcase the developed nanoparticles in the delivery of an FMS inhibitor to cells, resulting in inhibition of the FMS receptor. As such, this study lays the groundwork for further drug-delivery studies aimed at specifically targeting TAMs with molecularly targeted therapeutics.
Date Issued
2020-08-11
Date Acceptance
2020-07-27
Citation
ACS Applied Bio Materials, 2020, 3 (9), pp.5775-5786
ISSN
2576-6422
Publisher
American Chemical Society (ACS)
Start Page
5775
End Page
5786
Journal / Book Title
ACS Applied Bio Materials
Volume
3
Issue
9
Copyright Statement
© 2020 American Chemical Society. This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Applied Bio Materials, after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acsabm.0c00529
Sponsor
Engineering & Physical Science Research Council (EPSRC)
Identifier
https://pubs.acs.org/doi/10.1021/acsabm.0c00529
Grant Number
EP/R00188X/1
Publication Status
Published
Article Number
acsabm.0c00529
Date Publish Online
2020-07-28