title: Polymer-modified gadolinium metal-organic framework nanoparticles used as multifunctional nanomedicines for the targeted imaging and treatment of cancer.
abstract: Novel nanoscale theragnostic devices were successfully prepared through attachment of well defined, multifunctional polymer chains to gadolinium (Gd) metal-organic framework (MOF) nanoparticles. Copolymers of poly(N-isopropylacrylamide)-co-poly(N-acryloxysuccinimide)-co-poly(fluorescein O-methacrylate) were prepared via reversible addition-fragmentation chain transfer (RAFT) polymerization. The succinimide functionality was utilized as a scaffold for attachment of both a therapeutic agent, such as methotrexate, and a targeting ligand, such as H-glycine-arginine-glycine-aspartate-serine-NH(2) peptide. Employment of a trithiocarbonate RAFT agent allowed for reduction of the polymer end groups to thiolates providing a means of copolymer attachment through vacant orbitals on the Gd(3+) ions at the surface of the Gd MOF nanoparticles. These versatile, nanoscale scaffolds were shown to be biocompatible and have cancer cell targeting, bimodal imaging, and disease treatment capabilities. This unique method provided a simple yet versatile route of producing polymer-nanoparticle theragnostic materials with an unprecedented degree of flexibility in the construct, potentially allowing for tunable loading capacities and spatial loading of targeting/treatment agents, while incorporating bimodal imaging capabilities through both magnetic resonance and fluorescence microscopy.
authors.affiliation: Department of Chemistry and Geochemistry, Colorado School of Mines, Golden, Colorado 80401, USA.
authors.forename: Misty D
authors.initials: MD
authors.lastname: Rowe
authors.forename: Douglas H
authors.initials: DH
authors.lastname: Thamm
authors.forename: Susan L
authors.initials: SL
authors.lastname: Kraft
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Boyes
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D003952:Diagnostic Imaging; D004285:Dogs; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology; D005682:Gadolinium; D006131:Growth Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D008727:Methotrexate / Q000627:therapeutic use; D050997:Nanomedicine; D053758:Nanoparticles; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry*; D012509:Sarcoma / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000964:Antimetabolites, Antineoplastic; D006131:Growth Inhibitors; D011108:Polymers; D005682:Gadolinium; D008727:Methotrexate