Surface-Catalyzed Nitric Oxide Release via a Metal Organic Framework Enhances Antibacterial Surface Effects

Abstract

It has been previously demonstrated that metal nanoparticles embedded into polymeric materials doped with nitric oxide (NO) donor compounds can accelerate the release rate of NO for therapeutic applications. Despite the advantages of elevated NO surface flux for eradicating opportunistic bacteria in the initial hours of application, metal nanoparticles can often trigger a secondary biocidal effect through leaching that can lead to unfavorable cytotoxic responses from host cells. Alternatively, copper-based metal organic frameworks (MOFs) have been shown to stabilize Cu 2+/1+ via coordination while demonstrating longerterm catalytic performance compared to their salt counterparts. Herein, the practical application of MOFs in NO-releasing polymeric substrates with an embedded NO donor compound was investigated for the first time. By developing composite thermoplastic silicon polycarbonate polyurethane (TSPCU) scaffolds, the catalytic effects achievable via intrapolymeric interactions between an MOF and NO donor compound were investigated using the water-stable copper-based MOF H 3 [(Cu 4 Cl) 3 (BTTri) 8 -(H 2 O) 12 ]•72H 2 O (CuBTTri) and the NO donor Snitroso-N-acetyl-penicillamine (SNAP). By creating a multifunctional triple-layered composite scaffold with CuBTTri and SNAP, the surface flux of NO from catalyzed SNAP decomposition was found tunable based on the variable weight percent CuBTTri incorporation. The tunable NO surface fluxes were found to elicit different cytotoxic responses in human cell lines, enabling application-specific tailoring. Challenging the TSPCU−NO−MOF composites against 24 h bacterial growth models, the enhanced NO release was found to elicit over 99% reduction in adhered and over 95% reduction in planktonic methicillin-resistant Staphylococcus aureus, with similar results observed for Escherichia coli. These results indicate that the combination of embedded MOFs and NO donors can be used as a highly efficacious tool for the early prevention of biofilm formation on medical devices.

Metal organic framework-based antibacterial agents and their underlying mechanisms

“…Simultaneously, the existence of Cu could trigger the decomposition of SNAP, and then the flux of NO. 207 Besides Cu, SNAP could also be triggered by heat. Thus, when SNAP was combined with MOF@Au nanoparticles, which were photothermal, NO could be released on demand and killed the bacteria efficiently under light irradiation, as shown in Fig.…”

Recent Developments in Multifunctional Antimicrobial Surfaces and Applications toward Advanced Nitric Oxide-Based Biomaterials

“…To overcome the challenge of metal leaching, copper-based metal–organic frameworks (MOFs) have been reported to alleviate Cu 2+/1+ via coordination with extended catalytic operation as opposed to their salt or nanoparticle counterparts. The use of MOFs in NO-releasing polymeric composites with NO donor compounds was demonstrated by the creation of a multifunctional triple-layer composite scaffold with CuBTTri and SNAP . The NO release levels from the catalyzed SNAP decay could be finely tuned by varying the concentration of CuBTTri.…”

“…The use of MOFs in NO-releasing polymeric composites with NO donor compounds was demonstrated by the creation of a multifunctional triple-layer composite scaffold with CuBTTri and SNAP. 179 The NO release levels from the catalyzed SNAP decay could be finely tuned by varying the concentration of CuBTTri. These combinational NO-MOF surfaces demonstrated 2.74 and 1.23 log reduction in adhered MRSA and E. coli, respectively.…”

“…These combinational NO-MOF surfaces demonstrated 2.74 and 1.23 log reduction in adhered MRSA and E. coli, respectively. 179 Although these surfaces showed improved antibacterial properties compared with the individual NO or MOF control surfaces, the practical use of MOF-containing materials has been restricted because of high production rates, inadequate selectivity, minimal function, and complexities in recycling/regeneration. 180 Similar studies involving a combination of NO and a nanocomposite poly(vinylidene fluoride) (PVDF) membrane or other light-activated antibacterial nanomolecules have been reported.…”

Nitric Oxide-Releasing Platforms for Treating Cardiovascular Disease

“…Garren et al developed a multifunctional three-layer composite scaffold with H 3 [(Cu 4 Cl) 3 (BTTri) 8 -(H 2 O) 12 ]·72H 2 O and a NO donor, S-nitroso-N-acetylpenicillamine (SNAP). This scaffold exhibited enhanced NO release and had a good antibacterial effect, significantly reducing the adhesion of Staphylococcus aureus and Escherichia coli [ 83 ]. Copper ion (Cu II ) can promote the growth of ECs and increase the content of NO in vivo.…”