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.