Synthesis of Hybrid Inorganic/Organic Nitric Oxide-Releasing Silica Nanoparticles for Biomedical Applications

Nitric oxide (NO) is an endogenously produced free radical involved in a number of physiological processes. Thus, much research has focused on developing scaffolds that store and deliver exogenous NO. Herein, the synthesis of N-diazeniumdiolate-modified silica nanoparticles of various physical and chemical properties for biomedical applications is presented. To further develop NO-releasing silica particles for antimicrobial applications, a reverse microemulsion synthesis was designed to achieve nanoparticles of distinct sizes and similar NO release characteristics. Decreasing scaffold size resulted in improved bactericidal activity against Pseudomonas aeruginosa. Confocal microscopy revealed that the improved efficacy resulted from faster particle-bacterium association kinetics. To broaden the therapeutic potential of NO-releasing silica particles, strategies to tune NO release characteristics were evaluated. Initially, surface hydrophobicity and NO release kinetics were tuned by grafting hydrocarbon- and fluorocarbon-based silanes onto the surface of N-diazeniumdiolate-modified particles. The addition of fluorocarbons resulted in a 10x increase in the NO release half-life. The addition of short-chained hydrocarbons to the particle surface increased their stability in hydrophobic electrospun polyurethanes. Although NO release kinetics were longer than that of unmodified particles, durations were still limited to <7 days. An alternative strategy for increasing NO release duration involved directly stabilizing the N-diazeniumdiolate using O2-protecting groups. O2-Methoxymethyl 1-(4-(3-(trimethoxysilyl)propyl))piperazin-1-yl)diazen-1-ium-1,2-diolate (MOM-Pip/NO) was grafted onto mesoporous silica nanoparticles to yield scaffolds with an NO payload of 2.5 μmol NO/mg and an NO release half-life of 23 d. Doping the MOM-Pip/NO-modified particles into resin composites yielded antibacterial NO-releasing dental restorative materials. A 3-log reduction in viable adhered Streptococcus mutans was observed with the MOM-Pip/NO-doped composites compared to undoped controls. The greater chemical flexibility of macromolecular scaffolds is a major advantage over LMW NO donors as it allows for the incorporation of multiple functionalities onto a single scaffold. To demonstrate this advantage, dual functional particles were synthesized by covalently binding quaternary ammonium (QA) functionalities to the surface of NO-releasing silica particles. The QA functionality proved more effective against Staphylococcus aureus than P. aeruginosa, and increasing alkyl chain length correlated with increased efficacy. Nitric oxide-releasing QA-functionalized particles were found to be more effective against S. aureus compared to monofunctional particles.Doctor of Philosoph

The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project

The PREDICTS project—Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)—has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity