New biodegradable bisphosphonate vinylic monomers and near infrared fluorescent nanoparticles for biomedical applications

Abstract

Bisphosphonates (BPs) are non‐hydrolyzable pyrophosphate analogs with high affinity to hydroxyapatite due to their ability to create bidentate or tridentate chelates with calcium ions. Consequently, BP lead to strong interactions with dentin, enamel, and bones. BPs (especially those bearing OH) accelerate osteoblasts action, while strongly inhibiting osteoclasts, thus contributing to enhanced bone formation. Recently, several novel BP non‐biodegradable and biodegradable vinylic monomers were synthesized in our laboratory. This article provides a detailed description regarding the synthesis of a unique biodegradable BP monomer and near infrared (NIR) fluorescent nano/microparticles for diagnosis and therapy of bone malignancy. These particles were prepared by dispersion copolymerization of three monomers: methacrylate polyethylene glycol (PEG) BP, N‐(3‐aminopropyl) methacrylamide, and the crosslinker monomer tetra(ethyleneglycol) diacrylate. The PEG‐BP nanoparticles size was controlled by changing various polymerization parameters. These BP particles possess dual functionality: covalent attachment of a dye (e.g., NIR 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 hydroxyapatite through the BP groups belonging to the methacrylate PEG‐BP monomeric units. 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 all the organs except the bones decreased significantly within 48 h (p < 0.05) while that of the bones hardly changed over that time (p > 0.05). In addition, a relatively long half‐life time of these nanoparticles in blood has been demonstrated, probably due to the PEG moiety. Copyright © 2014 John Wiley & Sons, Ltd.