Theranostic Activity of Nitric Oxide-Releasing Carbon Quantum Dots.

The synthesis and anticancer cell activity of nitric oxide (NO)-releasing carbon quantum dots (CQDs) are described as potential theranostics. A series of secondary amine-modified CQDs were prepared using a hydrothermal method to modify ß-cyclodextrin with hydroxyl and primary amine terminal functional groups. Subsequent reaction of the CQDs with NO gas under alkaline conditions yielded N-diazeniumdiolate NO donor-modified CQDs with adjustable NO payloads (0.2-1.1 µmol/mg) and release kinetics (half-lives from 29 to 79 min) depending on the level of secondary amines and surface functional groups. The anticancer activity of the NO-releasing CQDs against Pa14c, A549, and SW480 cancer cell lines proved to be dependent on both NO payloads and surface functionalizations. Primary amine-modified CQDs with NO payloads ∼1.11 µmol/mg exhibited the greatest anticancer action. A fluorescence microscopy study demonstrated the utility of these NO-releasing CQDs as dual NO-releasing and bioimaging probes.

Nitric Oxide-Releasing Hyaluronic Acid as an Antibacterial Agent for Wound Therapy.

Taking advantage of their respective wound-healing roles in physiology, the dual activity of hyaluronic acid (HA) and nitric oxide (NO) was combined to create a single-agent wound therapeutic. Carboxylic acid groups of HA (6 and 90 kDa) were chemically modified with a series of alkylamines via carbodiimide chemistry to provide secondary amines for subsequent N-diazeniumdiolate NO donor formation. The resulting NO-releasing HA derivatives stored 0.3-0.6 µmol NO mg-1 and displayed diverse release kinetics (5-75 min NO-release half-lives) under physiological conditions. The 6 kDa HA with terminal primary amines and intermediate release kinetics exhibited broad-spectrum bactericidal activity against common wound pathogens, including planktonic methicillin-resistant Staphylococcus aureus as well as planktonic and biofilm-based multidrug-resistant Pseudomonas aeruginosa. The treatment of infected murine wounds with NO-releasing HA facilitated more rapid wound closure and decreased the quantity of the P. aeruginosa genetic material in the remaining wound tissue. Hyaluronidase readily degraded the HA derivatives, indicating that NO donor modification did not prohibit endogenous biodegradation pathways.

Orthogonal Ternary Functionalization of a Mesoporous Metal-Organic Framework via Sequential Postsynthetic Ligand Exchange.

A sequential postsynthetic ligand exchange process was used to prepare a series of mono-, di-, and trifunctionalized mesoporous metal-organic frameworks (MOFs). Using this process, orthogonal functional groups were installed and thereafter postsynthetically modified with dye and quencher molecules. Microspectrophotometry studies were used to determine the distribution of the two orthogonal functional groups within the MOF crystals.

Antibacterial activity of nitric oxide-releasing carboxymethylcellulose against periodontal pathogens.

The prevalence of periodontal disease poses a significant global health burden. Treatments for these diseases, primarily focused on removal and eradication of dental plaque biofilms, are challenging due to limited access to periodontal pockets where these oral pathogens reside. Herein, we report on the development and characterization of nitric oxide (NO)-releasing carboxymethylcellulose (CMC) derivatives and evaluate their in vitro bactericidal efficacy against planktonic Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, two prominent periodontopathogens. Bactericidal exposure assays revealed that three of the synthesized NO-releasing polymers were capable of reducing bacterial viability of both species by 99.9% in 2 hr at concentrations of 4 mg ml-1 or lower, reflecting NO's potent and rapid bactericidal action. The NO-releasing CMCs elicited minimal toxicity to human gingival fibroblasts at their bactericidal concentrations following 24-hr exposure.

Nitric Oxide-Releasing Macromolecular Scaffolds for Antibacterial Applications.

Exogenous nitric oxide (NO) represents an attractive antibacterial agent because of its ability to both disperse and directly kill bacterial biofilms while avoiding resistance. Due to the challenges associated with administering gaseous NO, NO-releasing macromolecular scaffolds are developed to facilitate NO delivery. This progress report describes the rational design and application of NO-releasing macromolecular scaffolds as antibacterial therapeutics. Special consideration is given to the role of the physicochemical properties of the NO storage vehicles on antibacterial or anti-biofilm activity.