Synthesis of Nitric Oxide-Releasing Silica Nanoparticles

Rothrock, Aaron R.; Donkers, Robert L.; Schoenfisch, Mark H.

doi:10.1021/ja0674338

Cited by 194 publications

(232 citation statements)

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“…NO induces S-nitrosylation of histone deacetylase 2, which leads to chromatin remodeling and significant inhibition of histone deacetylase activity [71]. Nitric oxide-releasing silica NPs have been successfully used for skin and soft tissue infection treatment [72] which suggests that in future, NO-releasing NPs might be commonly used as histone deacetylase inhibitors for epigenetic treatment of cancer.…”

Section: Epigenetic Toxicity Of Npsmentioning

confidence: 99%

Nanoparticle Technology as a Double-Edged Sword: Cytotoxic, Genotoxic and Epigenetic Effects on Living Cells

Jennifer¹,

Wnuk²

2013

JBNB

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Nanoparticles are considered as powerful tools in nanotechnological applications. Due to their unique physicochemical properties, their interactions with different biological systems have been shown. Nanomaterials have been successfully used as coating materials or treatment and diagnosis tools. Nevertheless, toxic effects of nanoparticles in vitro and in vivo have also been reported. Here, we summarize the current state of knowledge on exposure routes, cellular uptake and toxicological activities of the commonly used nanoparticles. In this context, we discuss the mechanisms of toxicity of nanoparticles involving perturbation of redox milieu homeostasis and cellular signaling pathways.

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Section: Epigenetic Toxicity Of Npsmentioning

confidence: 99%

Nanoparticle Technology as a Double-Edged Sword: Cytotoxic, Genotoxic and Epigenetic Effects on Living Cells

Jennifer¹,

Wnuk²

2013

JBNB

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“…Macromolecular scaffolds capable of effectively storing and releasing NO have been developed to enable local delivery (27,28). The most promising NO release vehicles to date include NO donor-modified N-diazeniumdiolate silica nanoparticles (29)(30)(31), dendrimers (32)(33)(34)(35)(36), and chitosan (15). While silica nanoparticles (14,(37)(38)(39) and dendrimers (32)(33)(34) are effective as antimicrobials, they do not easily break down and thus have limited potential as inhaled therapeutics.…”

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confidence: 99%

Antibacterial Action of Nitric Oxide-Releasing Chitosan Oligosaccharides against Pseudomonas aeruginosa under Aerobic and Anaerobic Conditions

Reighard

2015

Antimicrob Agents Chemother

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Chitosan oligosaccharides were modified with N-diazeniumdiolates to yield biocompatible nitric oxide (NO) donor scaffolds. The minimum bactericidal concentrations and MICs of the NO donors against Pseudomonas aeruginosa were compared under aerobic and anaerobic conditions. Differential antibacterial activities were primarily the result of NO scavenging by oxygen under aerobic environments and not changes in bacterial physiology. Bacterial killing was also tested against nonmucoid and mucoid biofilms and compared to that of tobramycin. Smaller NO payloads were required to eradicate P. aeruginosa biofilms under anaerobic versus aerobic conditions. Under oxygen-free environments, the NO treatment was 10-fold more effective at killing biofilms than tobramycin. These results demonstrate the potential utility of NO-releasing chitosan oligosaccharides under both aerobic and anaerobic environments. Pseudomonas aeruginosa is an opportunistic human pathogen that frequently colonizes people with compromised immune systems, such as those with cystic fibrosis (CF) or severe burn wounds (1). The success of P. aeruginosa as a pathogen is related to its multitude of virulence factors, which increase adherence to the host cells, induce inflammation, and disrupt the host immune response (1). Furthermore, P. aeruginosa is intrinsically resistant to many antibiotics due to low membrane permeability and increased expression of ␤-lactamases and efflux pumps (2-4). In addition to this native resistance, P. aeruginosa readily adapts to antibiotic challenge by acquiring resistance genes (3, 5) and forming protective, cooperative communities known as biofilms (6, 7).While all antibiotic resistance mechanisms are not fully understood, at least three main factors reduce antibiotic efficacy against bacterial biofilms compared to planktonic cells. First, P. aeruginosa in biofilms secretes a protective layer of exopolysaccharides that prevent the diffusion of antibiotics (7). In the context of cystic fibrosis, biofilm-bound P. aeruginosa exists predominantly as the mucoid phenotype, characterized by a secreted alginate matrix that provides a physical barrier against the host immune response and antibiotics (8). This exopolysaccharide matrix also prevents the diffusion of oxygen into biofilms, causing P. aeruginosa to switch from aerobic to anaerobic respiration (9). The reduced metabolic activity of P. aeruginosa undergoing anaerobic respiration protects the bacterium against traditional antibiotics that are most effective against rapidly dividing cells, including aminoglycosides and ␤-lactams (10, 11). Finally, biofilms produce persister cells (i.e., dormant bacteria that are highly resistant to chemical disinfectants and exhibit multidrug tolerance) much more frequently than planktonic bacterial cultures (3, 7).The failure of conventional antibiotics to treat P. aeruginosa biofilms and infections necessitates the development of new antibacterial agents. Nitric oxide (NO), an endogenously produced free radical that can disperse (12, 13) and ...

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“…To address delivery issues, Schoenfisch and coworkers have synthesized nanoparticle-based scaffolds capable of storing large payloads of NO. [16][17][18] The nanoparticles spontaneously release tunable levels of NO under aqueous conditions at physiological temperature and pH, and thus represent attractive vehicles for delivering NO. Nanoparticle delivery of NO has two main advantages over previously-developed small molecule NO donor systems (e.g., diazeniumdiolates, nitrosothiols, and metal-NO complexes 19,20 ).…”

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confidence: 99%

Bactericidal Efficacy of Nitric Oxide-Releasing Silica Nanoparticles

Hetrick

Shin²,

Stasko³

et al. 2008

ACS Nano

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The utility of nitric oxide (NO)-releasing silica nanoparticles as a novel antibacterial 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 bacteria, 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 advantage of delivering NO via nanoparticles for antimicrobial applications.Keywords nitric oxide; silica nanoparticle; antibacterial; bactericidal; cytotoxicity; reactive nitrogen species; reactive oxygen species Antibiotic resistance has resulted in bacterial infections becoming the most common cause of infectious disease-related death. 1,2 In the United States alone, nearly 2 million people per year acquire infections during a hospital stay, of which approximately 90,000 die. 2 The primary culprits behind such deadly infections are antibiotic-resistant pathogens, which are responsible for approximately 70% of all lethal nosocomial infections. The growing danger of life-threatening infections and the rising economic burden of resistant bacteria have created a demand for new antibacterial therapeutics.The use of nanoparticles as delivery vehicles for bactericidal agents represents a new paradigm in the design of antibacterial therapeutics. To date, most antibacterial nanoparticles have been engineered using traditional antibiotics that are either incorporated within the particle scaffold or attached to the exterior of the particle. In many cases, such particles have exhibited greater efficacy than their constituent antibiotics alone. For example, Gu et al. reported that vancomycin-capped gold nanoparticles exhibited a 64-fold improvement in efficacy over vancomycin alone. 3 Similarly, silver nanoparticles have schoenfisch@unc.edu. Supporting Information Available: Synthesis of FITC-modified silica nanoparticles, AFM analysis of nanoparticle dimensions, scavenging of NO by TSB, and confocal fluorescence microscopy images of PROLI/NO-treated P. aeruginosa cells. This material is available free of charge via the Internet at http://pubs.acs.org. NIH Public AccessAuthor Manuscript ACS Nano. Author manuscript; available in PMC 2013 February 13. shown greater antibacterial activity than silver ion (Ag + ) in solution due to the direct toxicity of the particles and tunable release of Ag + based on nanocomposite size. [4][...

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Synthesis of Nitric Oxide-Releasing Silica Nanoparticles

Cited by 194 publications

References 60 publications

Nanoparticle Technology as a Double-Edged Sword: Cytotoxic, Genotoxic and Epigenetic Effects on Living Cells

Nanoparticle Technology as a Double-Edged Sword: Cytotoxic, Genotoxic and Epigenetic Effects on Living Cells

Antibacterial Action of Nitric Oxide-Releasing Chitosan Oligosaccharides against Pseudomonas aeruginosa under Aerobic and Anaerobic Conditions

Bactericidal Efficacy of Nitric Oxide-Releasing Silica Nanoparticles

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