title: Near IR fluorescent conjugated poly(ethylene glycol)bisphosphonate nanoparticles for in vivo bone targeting in a young mouse model.
abstract: Bisphosphonate (BP) compounds are widely used in the treatment of bone disorders. This group of drugs with a high affinity to Ca(+2) ions is rapidly attracted to bone mineral, especially in areas of high resorption. We have engineered unique biodegradable BP nanoparticles (NPs) by dispersion co-polymerization of the monomers methacrylate-PEG-BP) and (3-Aminopropyl)mathacrylamide) with the crosslinker monomer tetra ethylene glycol diacrylate. These NPs possess a dual functionality: (1) covalent attachment of a dye (e.g. near IR dye) or a drug to the nanoparticles through the primary amine groups on the surface of the NPs; (2) chelation to the bone mineral hydroxyapatite through the BP on the surface of the NPs. This study describes the uptake of the unique near IR fluorescent Cy 7-conjugated BP NPs in bone of a young mouse model. Blood half-life studies revealed a relatively long half-life (approximately 5 h) due to a high concentration of PEG in the BP NPs as well as a relatively long whole body clearance (approximately 2 weeks). Body distribution studies showed a specific uptake of the BP NPs in bone. These unique engineered BP NPs are planned to be utilized in future work for diagnostic and drug delivery systems that are targeted to bone disorders.
authors.affiliation: Department of Chemistry, The Institute of Nanotechnology and Advanced Materials, Bar-Ilan University, 52900, Ramat Gan, Israel. safrar@gmail.com.
authors.forename: S
authors.initials: S
authors.lastname: Rudnick-Glick
authors.affiliation: Department of Chemistry, The Institute of Nanotechnology and Advanced Materials, Bar-Ilan University, 52900, Ramat Gan, Israel. enavcorem@gmail.com.
authors.forename: E
authors.initials: E
authors.lastname: Corem-Salkmon
authors.affiliation: Department of Chemistry, The Institute of Nanotechnology and Advanced Materials, Bar-Ilan University, 52900, Ramat Gan, Israel. grinbergigori@yahoo.com.
authors.forename: I
authors.initials: I
authors.lastname: Grinberg
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, 52900, Ramat Gan, Israel. ronenyehuda@gmail.com.
authors.forename: R
authors.initials: R
authors.lastname: Yehuda
authors.affiliation: Department of Chemistry, The Institute of Nanotechnology and Advanced Materials, Bar-Ilan University, 52900, Ramat Gan, Israel. shlomo.margel@mail.biu.ac.il.
authors.forename: S
authors.initials: S
authors.lastname: Margel
mesh_terms: D000375:Aging; D000818:Animals; D052160:Benzothiazoles / Q000378:metabolism; D001842:Bone and Bones / Q000502:physiology*; D002232:Carbocyanines / Q000378:metabolism; D004164:Diphosphonates / Q000737:chemistry*; D005260:Female; D005453:Fluorescence; D006207:Half-Life; D007259:Infrared Rays; D007275:Injections, Intravenous; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D053758:Nanoparticles / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D014018:Tissue Distribution
chemical_list: D052160:Benzothiazoles; D002232:Carbocyanines; D004164:Diphosphonates; D011092:Polyethylene Glycols; C011204:cyanine dye 7