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委托NIH开发针对辐射或核攻击的新医学对策。作为生物屏蔽项目的一部分，美国国立卫生研究院制定了一个研究目标，即开发新型放射性核素螯合和脱孔剂，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将全身放射性核素暴露降至最低。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着剂，它们在最大限度地减少有害物质进入人体内的吸收方面具有优势，从而减少清除放射性核素结合复合体的肾脏负担。在太平洋西北国家实验室(PNNL)，已经开发出一种新的纳米工程吸附剂--介孔载体材料上的自组装单分子膜(SAMs)，以促进从DCL地点发现的复杂废物中清除放射性核素。SAMMS材料是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创建的，已被证明是钚、Ne、铀、Am、放射性二化物、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。目前的提案侧重于将SAMMS的应用从其在环境清理中已被证明的效用扩大到其对人体放射性核素去孔化的效用。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)，用于急性暴露于放射性核素后的人体去孔化。该方法侧重于两个具体应用：(1)在胃肠道内螯合放射性核素，以限制摄入物质的全身吸收；(2)螯合从所有暴露途径(口服、经皮和吸入)全身吸收的血液中的放射性核素。预计拟议的实验将证明SAMMS对其他非靶标物种中的目标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度，有利的效益风险比，并且将以低成本获得，因此可以优于目前FDA批准的螯合疗法。一旦我们确定了SAMMS在放射性核素去孔化方面的有效性和安全性，候选SAMMS将获得FDA的许可，目标是加快部署，以在可能导致公共卫生紧急情况影响国家安全的核事故中保护公众。

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.