Journal of Polymer Science Part A: Polymer Chemistry, Vol.51, No.20, 4282-4291, 2013
Engineering of New Crosslinked Near-Infrared Fluorescent Polyethylene Glycol Bisphosphonate Nanoparticles for Bone Targeting
Bisphosphonates (BPs) are nonhydrolysable pyrophosphate analogs with high affinity to hydroxyapatite (HAP, bone mineral) and are mainly used for treatment of various bone diseases. In this study, we designed and prepared crosslinked BP nanoparticles by dispersion copolymerization of three monomers: methacrylate PEG bisphosphonate, N-(3-aminopropyl) methacrylamide, and tetra(ethylene glycol) diacrylate. The size and size distribution of these PEG-BP nanoparticles were controlled by changing various polymerization parameters. These BP particles possess dual functionality: covalent attachment of a dye (e.g., near IR fluorescent dye) or drug to the nanoparticles through the primary amine groups belonging to the aminopropyl methacrylamide monomeric units and chelation to the bone mineral HAP through the BP groups belonging to the methacrylate PEG bisphosphonate monomeric units, for enhanced long term bone-targeted imaging and therapy applications. Body distribution of the optimal crosslinked BP nanoparticles was tested on a chicken embryo model via intravenous administration. This study indicated that the fluorescence intensity of the all organs (e.g., blood, spleen, liver, kidney, and heart) except the bones decreased significantly within 48 h (p<0.05) while that of the bones hardly changed over that time (p>0.05). (c) 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 4282-4291
Keywords:nanoparticles;biopolymers;biological applications of polymers;bisphosphonates nanoparticles;near IR fluorescent nanoparticles