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

这个小企业创新研究（SBIR）第一阶段项目将开发一种富含胆固醇的仿生毒素纳米松，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撑的红细胞膜组成，可作为仿生诱饵来捕获和中和成孔毒素，而无论其分子结构如何。该平台可以解毒甲氧西林耐药金黄色葡萄球菌（MRSA）中的主要毒素α-溶血素，以及具有不同分子结构的其他毒素类型。为了将该平台转化为治疗毒素诱导的损伤和疾病，该I期项目旨在通过用胆固醇（许多成孔毒素的共同受体）富集该平台来增强纳米海绵的毒素结合亲和力，以更有效地去除毒素。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物种，大鼠和猪。该项目更广泛的影响/商业潜力在于纳米海绵的独特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膜损伤毒力因子，该平台具有显著的治疗潜力。此外，该平台还提供了一种独特的纳米结构，可以优雅地将生物材料与合成纳米材料连接起来。该项目的成功将为许多毒力因子带来一种有效的治疗选择，并为新兴的生物医学应用建立一类新的纳米颗粒。该计划将有利于抗毒素治疗领域以及一般的纳米技术研究。

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.