Synthesis and characterization of new poly(ethylene glycol)bisphosphonate vinylic monomer and non-fluorescent and NIR-fluorescent bisphosphonate micrometer-sized particles

Bisphosphonates (BPs) are non-hydrolysable pyrophosphate analogs with high affinity to hydroxyapatite (HAP, the main inorganic ingredient in bones) and are mainly used for bone diseases treatments. A new stable PEG-BP monomer and particles have been prepared for enhanced long term bone-targeted imaging and therapy applications. The new formed BP particles possess dual functionalities: chelation to the bone mineral, HAP, through the BP groups and covalent attachment of a dye or drug through primary amine groups. The BP particles showed no cytotoxic effect on human osteosarcoma cell lines and minor toxicity on mouse macrophage cells, indicating that these BP particles are good candidates for in vivo testing. The BP monomer and particles exhibited inhibition of HAP formation and dissolution, similar to a commercial Alendronate. Near IR (NIR) fluorescent BP particles were obtained by conjugation of Cy7-NHS ester to the primary amine groups of the BP particles. (C) 2012 Elsevier Ltd. All rights reserved.