Reversible addition fragmentation chain transfer (RAFT) polymerisation provides a highly controlled means to assemble copolymers of different architectures for a variety of applications, including drug delivery. Polymers consisting of a butyl methacrylate-co-methacrylic acid p(BMA-co-MAA) hydrophobic block and a poly(ethylene glycol) methyl ether methacrylate p(PEGMA-475) hydrophilic block were synthesised via RAFT polymerisation and self-assembled into micelles. A range of micelle particles of different sizes were obtained by varying the composition of the block copolymers. The micelles were crosslinked to form nanoparticles and fluorescently labelled to study cellular internalisation. The prepared nanoparticles were extensively taken up by primary murine macrophages and a promising candidate was identified. To demonstrate effective delivery of a cell impenetrable cargo a fluorescent dye, 4′,6-diamidino-2-phenylindole (DAPI), was encapsulated inside the nanoparticles and successfully delivered to macrophages. The nanoparticles’ stability at increased temperatures and at low concentrations, the tunability of their synthesis and their extensive internalisation by macrophages and performance makes them highly promising delivery vehicles for a range of therapeutics and imaging agents

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.