Glycosylated Nanoparticles Derived from RAFT Polymerization for Effective Drug Delivery to Macrophages

Abstract

The functional-group tolerance and simplicity of reversible addition fragmentation chain transfer (RAFT) polymerization enables 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 P(BMA-co-MAA) diblock, which were extended with a hydrophilic block, cross-linker and mannose-based monomer scaffold; exploiting the abundance of macrophage mannose receptors (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 macrophage mannose receptor (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.

Mannose Ligands for Mannose Receptor Targeting

“…These targeted NPs are biocompatible in vitro and in vivo at physiologically relevant doses, and thus, this study is the first to demonstrate mannose-conducted preferential mRNA delivery to TAMs in an in vivo model. Recently, Rushworth et al prepared a series of fluorescently labeled RAFT polymers based on a mannose monomer scaffold that can be assembled into mannosylated NPs and successfully internalized into macrophages via a macrophage MR [156].…”

Mucosomes: Intrinsically Mucoadhesive Glycosylated Mucin Nanoparticles as Multi‐Drug Delivery Platform

“…We observed that the size of mucosomes increases after 32 h of incubation with serum (133 ± 57 nm vs 308 ± 97 nm, Figure S2, Supporting Information), a result that can be attributed to the large serum proteins. [75] The formation of the biomolecular corona is not necessarily associated with the hindering of the interaction of glycosylated nanoparticles with glycan-binding biomolecules. [76] To perform biodistribution studies, mucosomes were loaded with a fluorescent dye suitable for in vivo imaging tests.…”