Development of Selective Nanoporous Sorbents for Radionuclide Decorporation

描述（由申请人提供）：卫生与公众服务部已责成NIH承担开发针对放射性或核攻击的新医学对策的使命。作为“生物盾牌”项目的一部分，NIH确立了一项研究目标，即开发新型放射性核素螯合剂和去污剂，以防止涉及放射性弥散装置（RDD）（例如脏弹）或核爆炸的恐怖袭击。该项目将侧重于新产品的开发和验证，以通过新型螯合材料最大限度地减少放射性核素的全身暴露。我们建议在动物（体内）和人类（体外）系统中开发和验证新的纳米工程固体吸附剂，其在最大限度地减少有害物质吸收到体内从而减少肾脏负担以清除放射性核素结合复合物方面优于其液体对应物。在太平洋西北国家实验室（PNNL），一类新的纳米工程吸附剂，自组装单分子层介孔载体（SAMMS）材料，已被开发出来，以促进从DCL站点发现的复杂废物中清除放射性核素。通过在高度有序的介孔二氧化硅上安装精心设计的有机部分而产生，SAMMS材料已被证明是钚、镎、铀、镅、放射性碘化物、铯和钴的高效螯合剂，所有这些通常都可以在核弹和RDD中找到。目前的建议侧重于将SAMMS的应用从其在环境清理方面的已证明的效用扩展到其在人体放射性核素消除方面的效用。该项目的总体目标是开发和验证SAMMS材料，并评估其毒性（如果有的话），以用于急性暴露于放射性核素后的人体排毒。该方法侧重于两个具体应用：（1）螯合胃肠道内的放射性核素，以限制摄入物质的全身吸收;（2）螯合血液中通过所有接触途径（口服、皮肤和吸入）全身吸收的放射性核素。预计所提出的实验将证明，SAMMS可以优于目前FDA批准的螯合疗法，因为它对其他非靶物质中的靶放射性核素具有更高的结合亲和力和选择性、更大的吸附容量和快速的吸附速率、有利的获益风险比，并且将以低成本获得。一旦我们确定SAMMS用于放射性核素消除的效率和安全性有所提高，候选SAMMS将获得FDA许可，目标是在可能导致影响国家安全的公共卫生紧急事件的核事故期间加速部署以保护公众。

DESCRIPTION (provided by applicant): The Department of Health and Human Services has charged NIH with the mission of developing new medical countermeasures against radiological or nuclear attacks. As part of Project Bioshield, NIH has established a research goal of developing novel radionuclide chelation and decorporation agents for protection against terrorist attacks that involve radiological dispersion devices (RDD), (e.g. dirty bombs) or nuclear detonations. This project will focus on new product development and validation to minimize systemic exposure to radionuclides through novel chelating materials. We propose to develop and validate in animal (in vivo) and human (in vitro) systems new nano-engineered solid sorbants, which have advantages over their liquid counterparts in minimizing the absorption of harmful agents into the body and thereby reducing the kidney burden for clearing the radionuclide-bound complex. At the Pacific Northwest National Laboratory (PNNL), a new class of nano-engineered sorbants, self-assembled monolayer on mesoporous supports (SAMMS) materials, has been developed to facilitate the cleanup of radionuclides from complex waste found at the DCL sites. Created by installation of well-designed organic moieties onto the highly ordered mesoporous silica, the SAMMS materials have been demonstrated to be highly effective chelators for plutonium, neptunium, uranium, americium, radiolodide, cesium and cobalt, all of which can be normally found in nuclear bombs and RDD. The current proposal focuses on extending the application of SAMMS from their proven utility in environmental clean-up to their utility for radionuclide decorporation in humans. The overall goal of this project is to develop and validate SAMMS materials, and evaluate their toxicity (if any) for use in decorporation of humans following acute exposures to radionuclides. The approach focuses on two specific applications: (1) to chelate radionuclides within the gastrointestinal tract in order to limit systemic absorption of ingested materials and (2) to chelate radionuclides in blood that have been absorbed systemically from all routes of exposure (oral, dermal and inhalation). It is anticipated that the proposed experiments will demonstrate that SAMMS can outperform current FDA-approved chelation therapies by having higher binding affinity and selectivity for the target radionuclides among other non-target species, larger sorption capacity and rapid sorption rate, favorable benefit to risk ratio, and will be available at low costs. Once we have established increased efficacy and safety of SAMMS for radionuclide decorporation, candidate SAMMS will be advanced towards FDA licensure, with a goal of accelerated deployment to protect the public during a nuclear incident that may cause a public health emergency affecting national security.