I-Corps: Polysaccharides functionalized with metal chelators to treat low level lead poisoning

I-Corps项目的更广泛影响/商业潜力是开发一种治疗方法，通过降低血液中的铅含量来治疗铅中毒。铅中毒仍然是一个重大的公共卫生问题，特别是在儿童中，其长期认知和生理后果是长期和重大的。最近的研究表明，即使是5微克/分升的水平也会对儿童的健康产生负面影响，导致学业成绩下降、智商下降、注意力相关行为问题、反社会行为，并可能导致12岁以上儿童的青春期延迟和肾功能下降。螯合剂是一种与金属结合以帮助消除金属的分子，使用螯合剂可以降低血铅水平。然而，螯合治疗仅适用于非常高的血铅水平（44微克/分升）。对于较低水平的铅中毒（≤44微克/分升），传统螯合剂治疗的益处不超过螯合剂本身副作用的风险。该技术利用天然生物分子结合铅，具有生物相容性和安全性。此外，所提出的更安全的重金属粘合剂可能已经扩大了临床用途，以清除体内其他有毒金属，以及环境上清除重金属环境污染物。这个I-Corps项目的基础是开发一种化学疗法，以结合和去除血液中的有毒金属，如铅。提出的技术是重金属粘合剂（螯合剂）和大糖分子（多糖）的化学组合。所提出的技术旨在保留螯合剂的金属结合功效，同时通过多糖骨架赋予螯合剂相容性。初步实验结果证实，所提出的粘合剂具有相当大的金属结合能力。此外，细胞培养和初步动物研究表明，与未经修饰的螯合剂相比，拟议的技术既具有生物相容性，又能够更快地从体内清除有毒金属。拟议技术的商业化可以改善健康结果并减少医疗保健支出。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

The broader impact/commercial potential of this I-Corps project is the development of a therapeutic to treat lead poisoning by reducing the levels of lead from the blood. Lead poisoning remains a major public health issue, especially in children, where the long-term cognitive and physiological consequences are long-lasting and significant. Recent research has indicated that even levels of 5 mcg/dL have negative health effects in children, resulting in decreased academic achievement, lower IQ scores, attention-related behavior problems, antisocial behaviors, and possibly delayed puberty and decreased kidney function for children older than 12 years. The administration of chelators, which are molecules that bind with metals to aid in their elimination, can reduce blood lead levels. However, chelation therapy is only indicated for very high blood lead levels ( 44 mcg/dL). For lower-level lead poisoning (≤ 44 mcg/dL), the benefits of traditional chelation therapy do not outweigh the risks of the side effects of the chelators themselves. The proposed technology uses natural biomolecules to bind lead, which is biologically compatible and safer. In addition, the proposed safer heavy metal binders may have expanded use clinically to remove other toxic metals from the body, as well as environmentally to remove heavy metal environmental contaminants.This I-Corps project is based on the development of a chemical therapeutic to bind and remove toxic metals such as lead from the blood. The proposed technology is a chemical combination of heavy metal binders (chelators) and large sugar molecules (polysaccharides). The proposed technology is designed to retain the metal binding efficacy of the chelator, while imparting compatibility to the chelator through the polysaccharide backbone. Initial lab results confirm that the proposed binders have substantial metal-binding capacity. In addition, cell culture and preliminary animal studies suggest that the proposed technology is both biocompatible and able to more rapidly clear toxic metals from the body as compared with unmodified chelators. Commercialization of the proposed technology may improve health outcomes and reduce healthcare expenditures.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.