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

光诱导沸石-亚硝酰基复合材料释放 NO：一种预防伤口感染的新型生物材料

• 批准号: 1105296
• 负责人: Pradip Mascharak
• 金额: $ 39万
• 依托单位: University of California-Santa Cruz
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1105296&HistoricalAwards=false
• 关键词: Light; Induced; NO; Release; Zeolite

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.

这项由材料研究部生物材料计划授予加州大学圣克鲁斯分校的奖项支持合作研究努力，开发一种基于沸石的新型一氧化氮(NO)输送平台，以对抗和预防各种耐药病原体引起的感染。PIS实验室开发的几种具有光活性的金属(如Mn、Fe和Ru)络合物将首先被负载到根据孔大小和形状选择的纳米/介孔铝硅酸盐中。研究方法将通过计算机辅助设计来指导，以更好地将非络合物匹配到孔隙中，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它们的有效笼化。然后，这些复合材料中的NO释放将通过使用非敏感电极的各种技术来确定。将仔细监测从复合材料中光释放的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观察的剂量效应。最后，通过用沸石-亚硝基粉末浸渍生物兼容材料(如羧甲基纤维素)的垫子，将开发出不同的绷带材料原型。这些设计的非递送生物材料的优点包括：a)根据需要通过光触发将NO选择性地递送到生物靶标；b)将光产物包裹在生物兼容沸石宿主的腔内，从而避免其副作用；以及c)有效地消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的耐药性)。这两个专业人员的密切互动以及他们的本科生和本科生对该项目的参与，预计将在生物学和材料化学的交界处进行跨学科培训。这两个非政府组织经常招收代表不足的少数族裔学生和大学学生。加州社区大学的少数民族理科学生在他们的实验室工作，这些活动预计将继续这一项目。医院外科单元出现的金黄色葡萄球菌相关感染，以及患者因植入物和假体细菌污染而产生的并发症已经达到令人震惊的水平，需要更高效的新抗菌平台。尽管一氧化氮(NO)的强抗菌作用已被证实，但由于缺乏按需工作的递送平台，将高通量的NO输送到生物靶标(如感染伤口)是不可能的。最近，在皮？S实验室合成了几种具有光活性的金属(金属亚硝基)络合物。负载在硅基矿物沸石纳米孔中的亚硝基络合物将是一种新型的无递送系统，可以在低功率可见光下触发。这种材料既可以直接作为粉末应用于感染部位，也可以作为绷带材料应用于感染部位，在光的控制下，(从亚硝基)光释放的NO可以减少细菌负荷。因此，建议的沸石-亚硝基复合材料将成为一种新的治疗平台，特别是为目前没有其他治疗方法的抗生素耐药性细菌设计的。该项目在教学、培训和外展计划方面的更广泛影响是在生物学和材料研究方面对大量研究生和本科生进行跨学科培训。PIs在通过不同的资助项目招收暑期学生方面有着良好的记录，如NSF REU/SURF、NIH Access和其他促进来自代表性不足群体的学生参与的项目。传播计划提供了在同行评议的期刊、会议报告和其他渠道上发表的细节。