Light-Induced NO Release from Zeolite-Nitrosyl Composites: A New Biomaterial for the Prevention of Wound Infections

该奖项由加州大学圣克鲁斯材料研究部生物材料项目授予，支持开发新型沸石基一氧化氮（NO）输送平台的合作研究工作，以对抗和预防各种耐药病原体引起的感染。在PI实验室中开发的金属（如Mn、Fe和Ru）的几种光活性NO络合物将首先装载到基于其孔径和形状选择的纳米/中孔铝硅酸盐中。研究方法将通过计算机辅助设计来指导，以更好地将NO-络合物装入孔中，并通过粉末X射线衍射，红外光谱，扫描电子显微镜和能量色散元素图谱来确定其有效的笼。从这些复合材料的NO释放，然后将确定通过各种技术采用NO敏感电极。将仔细监测从复合材料的光释放的NO对各种细菌菌落的影响，以确定通过菌落计数技术和显微镜的剂量效应。最后，将通过用沸石-亚硝酰粉末浸渍生物相容性材料如羧甲基纤维素的垫来开发不同的绷带材料原型。这些设计的NO递送生物材料的优点将包括：a）根据需要通过光触发将NO位点选择性递送至生物靶; B）将光产物截留在生物相容性沸石宿主的空腔内，从而避免它们的副作用;和c）有效根除各种耐药菌株的细菌负荷（因为病原体很少表现出对作为抗生素的NO的抗性）。两个PI的密切互动和他们的研究生和本科生在项目中的参与，预计将导致在生物学和材料化学的接口跨学科培训。这两个PI小组定期引进代表性不足的少数民族学生以及加州大学社区学院的少数民族学生在他们的实验室工作，这些活动预计将继续与这个项目。医院外科病房中出现的葡萄球菌相关感染以及患者体内植入物和假体细菌污染引起的并发症已经达到了令人震惊的程度，要求新的抗菌平台具有更高的效率。尽管已经确定了一氧化氮（NO）的强抗微生物作用，但是由于缺乏按需工作的递送平台，将高通量的NO递送到生物靶标（例如感染的伤口）是不可能的。 最近，几个光活性NO配合物的金属（金属亚硝基）已在PI？的实验室。将亚硝酰复合物负载到硅基矿物沸石的纳米孔中将是用低功率可见光触发的新型NO递送系统。这种材料可以直接作为粉末或在感染部位的绷带材料内施用，并且可以在光的控制下用光释放的NO（来自亚硝基）减少细菌负荷。因此，所提出的沸石-亚硝酰复合物将是一种新的治疗平台，特别是针对目前没有其他治疗方法的耐药细菌而设计的。该项目的教学、培训和推广方案的更广泛影响是在生物学和材料研究的界面上对大量研究生和本科生进行跨学科培训。PI在通过不同的资助项目（如NSF REU/SURF，NIH ACCESS和其他促进代表性不足的群体的学生参与的项目）招募暑期学生方面有着良好的记录。传播计划提供了在同行评审的期刊、会议介绍和其他渠道上发表的细节。

This award by the Biomaterials Program of the Division of Materials Research to the University of California Santa Cruz supports the collaborative research efforts in developing a novel zeolite-based nitric oxide (NO) delivery platform to combat and prevent infections arising from various drug-resistant pathogens. Several photoactive NO complexes of metals (such as Mn, Fe and Ru) developed in the PIs' laboratory will be first loaded into nano/mesoporous aluminosilicates selected on the basis of their pore size and shape. The research approach will be guided by computer-aided design to better fit the NO-complexes into the pores, and their effective caging will be determined by powder X-ray diffraction, infrared spectroscopy, scanning electron microscopy and energy dispersive elemental mapping. The NO release from these composites will then be determined by various techniques employing NO-sensitive electrodes. The effects of the photoreleased NO from the composites on various bacterial colonies will be carefully monitored to determine the dose effects by colony-counting techniques and microscopy. Finally, different bandage material prototypes will be developed by impregnating mats of biocompatible materials such as carboxymethyl cellulose with the zeolite-nitrosyl powders. The advantages of these designed NO-delivery biomaterials will include: a) site-selective NO delivery to biological targets upon demand via light-triggering; b) entrapment of the photoproducts within the cavities of the biocompatible zeolite host thus avoiding their side-effects; and c) effective eradication of bacterial loads of various drug-resistant strains (since pathogens seldom exhibit resistance to NO as the antibiotic). Close interaction of the two PIs and the involvement of their graduate and undergraduate students in the project are expected to lead in interdisciplinary training at the interface of biology and materials chemistry. Both PI groups regularly bring in underrepresented minority students as well as Univ. California-bound community college minority students in science to work in their laboratories, and these activities are expected to continue with this project.The emergence of Staph-related infections in the surgical units of hospitals and complications due to bacterial fouling of implants and prosthetics in patients have reached an alarming level, demanding new antimicrobial platforms with greater efficiency. Although the strong antimicrobial effects of nitric oxide (NO) have been established, delivery of high fluxes of NO to a biological target (such as an infected wound) has not been possible due to lack of delivery platforms that work upon demand. Recently, several photoactive NO complexes of metals (metal nitrosyls) have been synthesized in the PI?s laboratory. Nitrosyl complexes loaded into the nanopores of the silica-base mineral zeolites would be novel NO-delivery systems to be triggered with low-power visible light. Such materials could be applied either directly as powders or within bandage materials on infected sites and the bacterial loads could be reduced with photoreleased NO (from the nitrosyls) under the control of light. The proposed zeolite-nitrosyl composites will therefore be a new treatment platform, especially designed for antibiotic-resistant bacteria for which no other treatments are currently available. Broader impacts with respect to teaching, training and outreach programs of this project are in interdisciplinary training of a large number of graduate and undergraduate students at the interface of biology and materials research. The PIs have a strong track record in recruiting summer students through different funded programs such as NSF REU/SURF, NIH ACCESS and others that promote participation of students from underrepresented groups. The dissemination plan provides details for publication in peer reviewed journals, meeting presentations and other channels.