Engineering of a New Bisphosphonate Monomer and Nanoparticles of Narrow Size Distribution for Antibacterial Applications

[Image: see text] In recent years, many bacteria have developed resistance to commonly used antibiotics. It is well-known that calcium is essential for bacterial function and cell wall stability. Bisphosphonates (BPs) have high affinity to calcium ions and are effective calcium chelators. Therefore, BPs could potentially be used as antibacterial agents. This article provides a detailed description regarding the synthesis of a unique BP vinylic monomer MA-Glu-BP (methacrylate glutamate bisphosphonate) and polyMA-Glu-BP nanoparticles (NPs) for antibacterial applications. polyMA-Glu-BP NPs were synthesized by dispersion copolymerization of the MA-Glu-BP monomer with the primary amino monomer N-(3-aminopropyl)methacrylamide hydrochloride (APMA) and the cross-linker monomer tetra ethylene glycol diacrylate, to form cross-linked NPs with a narrow size distribution. The size and size distribution of polyMA-Glu-BP NPs were controlled by changing various polymerization parameters. Near-infrared fluorescent polyMA-Glu-BP NPs were prepared by covalent binding of the dye cyanine7 N-hydroxysuccinimide to the primary amino groups belonging to the APMA monomeric units on the polyMA-Glu-BP NPs. The affinity of the near-infrared fluorescent polyMA-Glu-BP NPs toward calcium was demonstrated in vitro by a coral model. Cytotoxicity, cell uptake, and antibacterial properties of the polyMA-Glu-BP NPs against two common bacterial pathogens representing Gram-negative bacteria, Escherichia coli and Pseudomonas aeruginosa, and two representing Gram-positive bacteria, Listeria innocua and Staphylococcus aureus, were then demonstrated.