SBIR Phase I: Development of Biomimetic Toxin Nanosponges with Enhanced Toxin Affinity

这项小型企业创新研究（SBIR）一期项目将开发一种富含胆固醇的仿生毒素纳米粒，该纳米粒具有增强的毒素结合亲和力，可有效清除血液中的细胞溶解毒素。毒素纳米海绵由纳米颗粒支持的红细胞膜组成，作为一种仿生诱饵，可以阻止和中和形成孔的毒素，而不管它们的分子结构如何。该平台可以解毒耐甲氧西林金黄色葡萄球菌（MRSA）的主要毒素-溶血素，以及其他不同分子结构的毒素类型。为了将该平台转化为毒素诱导的损伤和疾病的治疗，该I期项目旨在通过在纳米海绵中添加胆固醇（许多成孔毒素的常见受体）来增强其毒素结合的亲和力，从而更有效地去除毒素。该项目还将毒素纳米海绵平台从现有的小鼠血液模型扩展到另外两种非人类动物，大鼠和猪。该项目更广泛的影响/商业潜力在于纳米海绵独特的仿生特性及其对多种成孔毒素类型的广泛适用性。由于细菌和动物毒液中广泛存在破坏膜的毒力因子，该平台具有显著的治疗潜力。此外，该平台还呈现出独特的纳米结构，可以优雅地将生物材料与合成纳米材料连接起来。该项目的成功将带来一种针对许多毒力因素的有效治疗选择，并为新兴的生物医学应用建立一类新的纳米颗粒。这个项目将有利于抗毒素治疗领域以及纳米技术的研究。

This Small Business Innovation Research (SBIR) Phase I project will develop a cholesterol-enriched biomimetic toxin nanopsonges with enhanced toxin-binding affinity for efficient scavenging of cytolytic toxins in the bloodstream. Consisting of nanoparticle-supported red blood cell membranes, toxin nanosponges serve as a biomimetic decoy to arrest and neutralize pore-forming toxins regardless of their molecular structures. The platform can detoxify alpha-hemolysin, a major toxin in methicillin-resistant Staphylococcus aureus (MRSA), as well as other toxin types with different molecular structures. Toward translating the platform to treatment of toxin-induced injuries and diseases, this Phase I project aims to enhance the toxin-binding affinity of the nanosponges for more efficient toxin removal by enriching the platform with cholesterol, a common receptor for many pore-forming toxins. The project also serves to expand the toxin nanosponge platform from the existing mouse blood model to two other non-human animal species, rat and pig. The broader impact/commercial potential of this project lies in the unique biomimetic properties of the nanosponges and its broad applicability against multiple pore-forming toxin types. The platform possesses significant therapeutic potential owing to broad presence of membrane-damaging virulence factors in bacteria and in animal venoms. In addition, the platform presents a unique nanostructure that elegantly bridges biological materials with synthetic nanomaterials. The success of the project will bring forth a potent therapeutic option against many virulence factors and establish a new class of nanoparticulate for emerging biomedical applications. This program will benefit the field of antitoxin treatment as well as nanotechnology studies in general.