Novel bisphosphonates near infrared fluorescent and non-fluorescent nanoparticles of narrow size distribution for bone targeting

Bisphosphonates (BPs) are a group of organophosphorus compounds which are used in the treatment of various bone related diseases. BPs possess a high affinity to the calcium in bone and thus can be used for bone targeting. Nanoparticles (NPs) are being developed as in-vivo targeted drug delivery systems. In this article, we report the synthesis and characterization of a new bisphosphonate vinylic monomer MAGlu- BP (methacrylate glutamate bisphosphonate) prepared by interacting methacryloyl chloride with gGlu-BP. Non-fluorescent crosslinked bisphosphonate NPs of narrow size distribution were then prepared by dispersion co-polymerization of MA-Glu-BP with a vinylic monomer containing primary amino group, N-(3-aminopropyl) methacrylamide (APMA) and a crosslinker vinylic monomer, tetra ethylene glycol diacrylate (TTEGDA). Near infra-red (NIR) fluorescent crosslinked bisphosphonate NPs were then prepared by covalent conjugation of the NIR dye Cy-7 to the primary amino groups belonging to the APMA monomeric units of the non-fluorescent bisphosphonate NPs. The affinity of the poly(MA-Glu-BP) NPs to calcium was illustrated by interacting the NIR fluorescent poly(MA-Glu-BP) NPs with hydroxyapatite. (C) 2017 Elsevier Ltd. All rights reserved.