Polymer-Modified Nanoparticles as Targeted MR Imaging Agents

Abstract

AbstractA novel surface modification technique was employed to produce a polymer-modified, positive contrast agent nanoparticle for targeted magnetic resonance imaging (MRI). A range of both hydrophilic and hydrophobic homopolymers, along with novel multifunctional copolymers of poly(N-(2-hydroxypropyl) methacrylamide)-co-poly(N-methacryloxysuccinimide)-co-poly(fluorescein O-methacrylate), were synthesized using reversible addition-fragmentation chain transfer (RAFT) polymerization. These polymers were subsequently used to modify the surface of gadolinium (Gd) metal-organic framework (MOF) nanoparticles. The succinimide functionality of the copolymer was utilized as a scaffold for attachment of the targeting ligands, H-glycine-arginine-glycine-aspartate-serine-NH2 peptide or the antibody for epidermal growth factor. Reduction of the trithiocarbonate RAFT polymer end groups to thiolates provided a means of polymer attachment through vacant orbitals on the Gd3+ ions at the surface of the Gd MOF nanoparticles. MRI confirmed that the relaxivity rates of these novel polymer-modified structures were easily tuned by changes in size and shape of the nanoparticles or by modifying the molecular weight and chemical structure of the polymers attached to the surface of the nanoparticles. In most cases, the relaxivity values were significantly higher than both the unmodified Gd MOF nanoparticles and the clinically employed contrast agents, Magnevist® and MultiHance®. These versatile, polymer-modified nanoscale scaffolds were shown to provide biocompatibility, cancer cell targeting, and diagnostic imaging through positive contrast in MRI and fluorescence microscopy. This unique method provided a simple yet versatile route of producing polymer-modified nanoparticles for targeted MRI of cancer with an unprecedented degree of flexibility in the construct, potentially allowing for tunable loading capacities and spatial loading of targeting agents while incorporating bimodal imaging capabilities.KeywordsContrast AgentImaging AgentMagnetic Resonance Imaging Contrast AgentWormlike MicelleRaft AgentThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.