School of Chemical, Materials and Biomedical Engineering, College of Engineering, University of Georgia, Athens, Georgia 30602, United States.
Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523, United States.
ACS Appl Mater Interfaces. 2021 Dec 8;13(48):56931-56943. doi: 10.1021/acsami.1c17248. Epub 2021 Nov 24.
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 via coordination while demonstrating longer-term 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[(CuCl)(BTTri)-(HO)]·72HO (CuBTTri) and the NO donor -nitroso--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 , with similar results observed for . 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.
先前已经证明,将金属纳米粒子嵌入掺杂有一氧化氮(NO)供体化合物的聚合物材料中,可以加速 NO 的释放速度,从而实现治疗应用。尽管提高 NO 表面通量有利于在应用初期消除机会性细菌,但金属纳米粒子往往会通过浸出引发二次杀菌作用,从而导致宿主细胞产生不利的细胞毒性反应。或者,铜基金属有机框架(MOFs)已被证明通过配位稳定 Cu,同时与它们的盐对应物相比表现出更长的催化性能。在此,首次研究了将 MOF 应用于嵌入 NO 供体化合物的释放 NO 的聚合物基质中的实际应用。通过开发复合热塑性硅聚碳酸酯聚氨酯(TSPCU)支架,使用水稳定的铜基 MOF H[(CuCl)(BTTri)-(HO)]·72HO(CuBTTri)和 NO 供体 -亚硝酰基-乙酰-青霉胺(SNAP)研究了 MOF 与 NO 供体化合物之间的聚合物内相互作用可实现的催化作用。通过创建具有 CuBTTri 和 SNAP 的多功能三层复合支架,发现基于 CuBTTri 掺入的可变重量百分比,可以调节由催化 SNAP 分解产生的 NO 的表面通量。发现可调谐的 NO 表面通量会引起人细胞系产生不同的细胞毒性反应,从而实现特定于应用的定制。将 TSPCU-NO-MOF 复合材料与 24 h 细菌生长模型进行对比,发现增强的 NO 释放可使附着的减少超过 99%,浮游的减少超过 95%,对耐甲氧西林金黄色葡萄球菌也是如此,对耐万古霉素肠球菌也观察到了类似的结果。这些结果表明,嵌入的 MOFs 和 NO 供体的组合可用作医疗设备上生物膜形成的早期预防的高效工具。