Mechanistic aspects of the reactions of nitric oxide with transition-metal complexes.

The utility of nitric oxide (NO)-releasing silica nanoparticles as novel antibacterial agents is demonstrated against Pseudomonas aeruginosa. Nitric oxide-releasing nanoparticles were prepared via co-condensation of tetraalkoxysilane with aminoalkoxysilane modified with diazeniumdiolate NO donors, allowing for the storage of large NO payloads. Comparison of the bactericidal efficacy of the NO-releasing nanoparticles to 1-[2-(carboxylato)pyrrolidin-1-yl]diazen-1-ium-1,2-diolate (PROLI/NO), a small molecule NO donor, demonstrated enhanced bactericidal efficacy of nanoparticle-derived NO and reduced cytotoxicity to healthy cells (mammalian fibroblasts). Confocal microscopy revealed that fluorescently labeled NO-releasing nanoparticles associated with the bacterial cells, providing rationale for the enhanced bactericidal efficacy of the nanoparticles. Intracellular NO concentrations were measurable when the NO was delivered from nanoparticles as opposed to PROLI/NO. Collectively, these results demonstrate the...

Bactericidal efficacy of nitric oxide-releasing silica nanoparticles

Diabetes mellitus is a worldwide epidemic characterized by chronic hyperglycemia that results from either a deficiency or tolerance in insulin.1 In the United States, 8.3% of the population currently has diabetes and that number is projected to increase to 1 in 3 adults by 2050 if current trends continue.2 As a consequence, diabetes is the seventh leading cause of death with an annual cost burden of $174 billion in the United States, including $116 billion in direct medical expenses.2 Blood glucose levels in diabetics fluctuate significantly throughout the day, resulting in serious complications including heart attacks, strokes, high blood pressure, kidney failure, blindness and limb amputation.1–2 Portable glucose sensors give patients the ability to monitor blood glucose levels, manage insulin levels, and reduce the morbidity and mortality of diabetes mellitus. Traditional glucose monitoring techniques are primarily based on the use of electrochemical amperometric glucose sensors. In 1987, Medisense Inc. launched the first personal glucose testing device consisting of a test strip and reader. Over 40 different commercial pocket-sized monitors have been introduced since then.3 To date, the U.S. Food and Drug Administration (FDA) has approved >25 glucose monitors with the majority employing test strips consisting of either glucose dehydrogenase (GDH) or glucose oxidase (GOx) immobilized on a screen-printed electrode.4 The analysis is based on obtaining a small blood sample (<1 μL) through a finger prick that is subsequently introduced into the test strip via capillary action.3–4 While these monitors have augmented the health outcomes for people with diabetes by improving blood glucose management, such monitoring only provides instantaneous blood glucose concentrations that are unable to warn of hyperglycemic or hypoglycemic events in advance. Additionally, the sample collection (i.e., finger prick) method is inconvenient resulting in poor patient compliance. Analytical methods that enable continuous monitoring of blood glucose have thus been sought.5 Continuous glucose monitoring (CGM) provides real-time information on trends (i.e., whether the glucose levels are increasing or decreasing), magnitude, duration, and frequency of glucose fluctuations during the day.5–6 Ideally, analytically functional continuous glucose monitoring devices could be linked to an insulin delivery pump, creating an artificial pancreas.5–6 In this review, we describe progress in the development of continuous glucose monitoring technologies, specifically focusing on subcutaneous implantable electrochemical glucose sensors, which are widely studied and commercially available. We discuss the challenges associated with the development of biocompatible coatings for electrochemical glucose sensors. Borrowing from the ideas of David Williams, we consider sensor coatings to be “biocompatible” if they optimize the clinical relevance of the sensor, avoid any negative local and systemic effects, and elicit the most appropriate local tissue response adjacent to the implant.7

/pdf/biocompatible-materials-for-continuous-glucose-monitoring-xpkx2iwy44.pdf

Biocompatible materials for continuous glucose monitoring devices.

The development of cancer cell resistance to various cytotoxic stimuli continues to be a major challenge in oncology and novel therapeutic approaches are urgently needed. Nitric oxide (NO) is emerging as a potential anti-oncogenic agent to overcome tumor cell resistance to conventional therapeutic agents. NO is a ubiquitous, water-soluble, free radical gas that exerts a wide range of biological effects. The actions of nitric oxide are highly variable in oncology with reports in the literature on both sides of the spectrum as an anti-neoplastic vs. a pro-neoplastic agent. The final activity of NO in oncology is dependent on its working microenvironment, including the type of cell exposed to the compound, the redox state of the reaction, as well as the final intracellular concentration and the duration of intracellular exposure to nitric oxide. There is, however, no unifying mechanistic explanation for the biphasic role of nitric oxide in oncology. Nitric oxide donors mimic continuous production of NO in a wide range of time intervals (seconds to days). Thus, multiple biological and (pro- vs. anti-) neoplastic responses are elicited from NO donors depending on the half-life and the type of cell exposed to the compound. The large variety of nitric oxide donors may serve as a tool to explore the wide range of oncologic properties of NO in cancer. In the present report, we discuss classic nitric oxide donors and their potential therapeutic roles as cytotoxic agents or chemo-radio or -immune-sensitizing compounds in the treatment of drug-resistant cancers.

https://www.spandidos-publications.com/10.3892/ijo_00000079/download

Nitric oxide donors: novel cancer therapeutics (review).

Nitric oxide-releasing sol–gels as antibacterial coatings for orthopedic implants

Diazeniumdiolate ions of structure R2N[N(O)NO]- (1) are of pharmacological interest because they spontaneously generate the natural bioregulatory species, nitric oxide (NO), when dissolved in aqueous media. Here we report the kinetic details for four representative reactivity patterns:  (a) straightforward dissociation of the otherwise unfunctionalized diethylamine derivative 2 (anion 1, where R = Et) to diethylamine and NO; (b) results for the zwitterionic piperazin-1-yl analogue 4, for which the protonation state of the neighboring basic amine site is an important determinant of dissociation rate; (c) data for 5, a diazeniumdiolate derived from the polyamine spermine, whose complex rate equation can include terms for a variety of medium effects; and (d) the outcome for triamine 6 (R = CH2CH2NH3+), the most stable structure 1 ion identified to date. All of these dissociations are acid-catalyzed, with equilibrium protonation of the substrate preceding release of NO. Specific rate constants and pKa values ...

and Joseph E. Saavedra

Papers

Chemistry of the diazeniumdiolates. 2. Kinetics and mechanism of dissociation to nitric oxide in aqueous solution.