TY - GEN
T1 - Surface modification of positive contrast Nanoparticle agents with RAFT polymers towards the targeted imaging and treatment of cancer
AU - Boyes, Stephen G.
AU - Rowe, Misty D.
AU - Chang, Chia Chih
AU - Thamm, Douglas H.
AU - Kraft, Susan L.
AU - Harmon, Joseph F.
AU - Serkova, Natalie J.
AU - Vogt, Andrew P.
AU - Sumerlin, Brent S.
PY - 2010/11/17
Y1 - 2010/11/17
N2 - A novel surface modification technique was employed to produce a polymer modified positive contrast agent nanoparticle through attachment of well defined polymers synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. A range of both hydrophilic and hydrophobic RAFT homopolymers, along with novel multifunctional copolymers of poly(N-isopropylacrylamide)-co-poly(Nacryloxysuccinimide)- co-poly(fluorescein O-methacrylate) were synthesized and 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 therapeutic agent, methotrexate, and targeting ligand, H-glycine-arginine- glycine-aspartate-serine-NH2 peptide. Reduction of the trithiocarbonate RAFT polymer end groups under basic conditions to thiolates provided a means of polymer attachment through vacant orbitals on the Gd 3+ ions at the surface of the Gd MOF nanoparticles. Magnetic resonance imaging (MRI) confirmed the relaxivity rates of these novel polymer modified structures were easily tuned by changes in the molecular weight and chemical structures of the polymers. 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, diagnostic imaging, through positive contrast in MRI and fluorescence microscopy, 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.
AB - A novel surface modification technique was employed to produce a polymer modified positive contrast agent nanoparticle through attachment of well defined polymers synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. A range of both hydrophilic and hydrophobic RAFT homopolymers, along with novel multifunctional copolymers of poly(N-isopropylacrylamide)-co-poly(Nacryloxysuccinimide)- co-poly(fluorescein O-methacrylate) were synthesized and 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 therapeutic agent, methotrexate, and targeting ligand, H-glycine-arginine- glycine-aspartate-serine-NH2 peptide. Reduction of the trithiocarbonate RAFT polymer end groups under basic conditions to thiolates provided a means of polymer attachment through vacant orbitals on the Gd 3+ ions at the surface of the Gd MOF nanoparticles. Magnetic resonance imaging (MRI) confirmed the relaxivity rates of these novel polymer modified structures were easily tuned by changes in the molecular weight and chemical structures of the polymers. 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, diagnostic imaging, through positive contrast in MRI and fluorescence microscopy, 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.
UR - http://www.scopus.com/inward/record.url?scp=84866086623&partnerID=8YFLogxK
U2 - 10.1021/bk-2010-1053.ch004
DO - 10.1021/bk-2010-1053.ch004
M3 - Conference contribution
AN - SCOPUS:84866086623
SN - 9780841225831
T3 - ACS Symposium Series
SP - 65
EP - 101
BT - Polymeric Delivery of Therapeutics
PB - American Chemical Society
ER -
