Development of a laboratory XANES system for the analysis of metals in tissue for cancer research and chemotherapy drug development

Project Summary Abstract Due to recent major advances in understanding platinum chemotherapy drugswhich are used to treat an estimatedof cancer patientsa new frontier of metal based anti cancer drugs is emergingMany promising novel metal based drugse gRuCoAuSnetcand several new formulations of platinum prodrugs are now being investigated as replacements for conventional platinum therapiesThese alternatives hold significant potential for overcoming the well known disadvantages of current Pt based chemotherapyincluding the development of patient resistance and toxicity to non tumorous tissueincluding hair fall out and damage to vital organs such as the kidney and brainX ray absorption near edge spectroscopyXANESis a powerful chemical analysis technique used to investigate the local atomic structure of these drugsThe electron structure of these new metal based chemotherapy drugs is critical to their performanceincludingintracellular activation in tumorous cellstransportation to the tumoractivityand lifetime of the drugHoweverthese drugs exist in low concentrations in biological tissue and currentlyXANES analysis requires researchers to travel to synchrotron light sourceswhich generate intense beams of x rays but of which there are just a handfulas they cost $ B to build and$M year to operateSynchrotron XANES systems are often extremely oversubscribedwith up to amonth application process and some beamlines limiting groups to a single run per yearall of which significantly limit access and the rate of research progressWe propose to develop a laboratory XANES system that utilizes a combination of breakthrough innovations to bring access to the capabilities of synchrotron based XANES to laboratories worldwideThe system is expected to critically enable research in novel metal based anti cancer drugsin addition to emerging research on the role of trace metal chemistry in pathologies including cancerThe proposed Phase Imonth project is a proof of principle demonstration of the advantages stemming from the x ray optic and geometry in a breadboard prototypeThe proposed Phase IImonth project is to develop a complete prototype Project Narrative This project proposes to develop a laboratory x ray absorption near edge spectroscopyXANESsystem optimized to address major questions in novel anti cancer metal based chemotherapyXANES enables understanding of the local atomic state of elementsa capability that is not easily accessible to the broader research community because it currently requires travel to one of the handful of synchrotron facilities located around the world thatdue to oversubscriptionprovide only limited accessBringing XANES to laboratories would not only have an immense impact on significantly accelerating metal based anti cancer drug developmentbut is also expected play a major role in emerging research on the role of metals in critical biological functions and in pathologies such as neurodegenerative diseases and cancer