Eradication of Pathogenic Bacteria by Remote Delivery of NO via Light Triggering of Nitrosyl-Containing Materials

Abstract

Although nitric oxide (NO) delivery systems have been fabricated with sol-gel-based materials, remote control of such systems with light has not been achieved. In this work, a fiber optic-based NO delivery system is described in which the photoactive metal-nitrosyl, [Mn(PaPy3)(NO)]ClO4 (1), has been employed in a sol-gel material. The material (1•FO) contains the manganese-nitrosyl which releases NO upon illumination with visible light. The NO-releasing capacity of 1•FO has been measured with an NO-sensitive electrode and the spatial diffusion of NO in solution has been visualized using the Griess reaction. The utility of 1•FO has been demonstrated in effective reduction of bacterial loads of Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus (MRSA). The results suggest that a device that releases NO via illumination by optical fiber may have clinical applications in combating infections with both Gram-positive, Gram-negative and to some degree antibiotic resistant bacteria.

Sustained Nitric Oxide-Releasing Nanoparticles Interfere with Methicillin-Resistant Staphylococcus aureus Adhesion and Biofilm Formation in a Rat Central Venous Catheter Model

“…Remarkably, NO-np reduced the viability of biofilm-related bacteria formed by multiple S. aureus clinical isolates, suggesting that this gas can penetrate the EPM to deliver its bactericidal properties. Similar levels of NO efficacy against multidrug-resistant bacteria within biofilms using different synthetic compounds (e.g., N-diazeniumdiolates [21,25], nitrosothiols [24], and nitrosyl metal complexes [22]) have been described. However, these studies showed certain limitations, such as the inability to chemically stabilize and release NO in a controlled manner, safety issues, and perhaps most important, not using multiple strains of a specific bacterial genus to address the variability observed from strain to strain in these types of experiments, hindering the possibility that the methods can be exploited in biomedical applications.…”

“…Our group has previously characterized and extensively demonstrated the therapeutic potential of NO generated and delivered by a siliconbased nanoparticle platform (NO-np) for the treatment of diverse infectious diseases, including Gram-positive and -negative bacterial and fungal skin and soft tissue infections (16)(17)(18)(19)(20). While a number of NO-donating compounds have emerged, been evaluated in vitro, and shown efficacy against biofilm-forming pathogens, many suffer from various limitations ranging from inadequate release capacity to stability and safety concerns (21)(22)(23)(24)(25). A defining feature of the NO-np is that it is a true NO generator, not an NO-donating compound with potential cytotoxicity, such as is seen with diazeniumdiolates (21,25).…”

The nature of Ru–NO bonds in ruthenium tetraazamacrocycle nitrosyl complexes—a computational study

“…39 Although the slow NO release may narrow some biological applications, such as improving the population spike of neurons, 39 it can act as a prodrug for vasodilation with slow blood pressure decrease, as observed in hypertensive male Wistar rats. 19 On replacing cyclam with four amine ligands the resulting ruthenium tetraamine nitrosyl complexes, 3 ), 4-picoline (4-pic), 4-chloropyridine (4-Clpy), imidazole (imC or imN), 4-acetylpyridine (4-acpy) and L-histidine (L-hist)) and k −NO can be tuned by a judicious choice of the trans ligand L. [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] In previous theoretical studies we have addressed this issue. 54,55 Unlike Thus, N-(or C-) functionalization could be a suitable approach to control the reactivity of coordinated NO.…”

Light‐Activated Release of Nitric Oxide with Fluorescence Reporting in Living Cells

“…[4] This inorganic radical is a biological mediator in many physiological processes, including neurotransmission, hormone secretion and vasodilatation. [5] Furthermore, NO has proven to reduce radical-mediated oxidative processes, [6] exert cytotoxic effects against infective microorganisms, [7] and inhibit tumor growth. [8] This multifaceted role has stimulated a massive interest in developing NO-releasing systems with the prospect to tackle important diseases.…”