A Novel Magnetic Separation Method to Isolate Active Compounds from Complex Matrices

天然产物富含生物活性（生物活性）化合物，是药物发现的重要来源。从天然产物中筛选药物先导物的主要挑战之一是缺乏有效的工具来识别和分离生物活性化合物。该项目将开发和表征一种新的磁分离方法，该方法基于细胞膜封装的氧化铁超颗粒（纳米颗粒簇），用于从天然产物中分离和鉴定生物活性化合物。该方法克服了传统方法成本高、耗时长的局限性，以及磁珠分离技术的非特异性结合问题。新方法也广泛适用于许多不同类型的跨膜药物靶点。该项目的成功将推动从复杂样品中识别和提取新药先导物的工业进程。该项目的影响将通过学生主导的教育和外展活动进一步增强，包括：(a)为本科生研究人员建立目标导向的培训机制和相关课程；(b)制定一个以数学概念建设为重点的STEM先导计划。将开发的具体科学推广项目是针对科学中学的奥林匹克训练模块和通过“儿童科学派对”计划针对小学生的磁性钓鱼实验。本项目的目的是开发一种基于细胞膜封装氧化铁超颗粒（CSMPs）的新型磁分离方法，用于鉴定和分离天然产物中的生物活性化合物。CSMPs将具有固定化的细胞膜，具有全功能的受体，允许识别特异性结合跨膜受体的化合物。磁性超粒子完全封装在细胞膜内，克服了目前磁珠分离技术的非特异性结合问题。磁性超粒子的使用可以快速识别和提取针对跨膜蛋白的化合物。CSMP方法也很容易转化为不同的跨膜蛋白靶点，这大大拓宽了该分离技术的适用性。为了实现总体目标，pi将开发、表征和评估CSMP方法，该方法使用带有功能性尼古丁受体的细胞膜来有效识别人工混合物（已知的粘合剂和非粘合剂）和香烟烟雾凝聚物中的结合化合物。该技术将使用具有功能瞬时受体电位（TRP）通道（例如，TRPV1）和电压门控钠通道的细胞膜进一步验证。这两种类型的受体已被证明是开发新型镇痛药物的有效靶点。该项目的成果将是与从复杂基质中有效分离生物活性化合物相关的基础知识。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。

Natural products are rich in biologically active (bioactive) compounds and serve as great sources for drug discovery. One of the major challenges in screening drug leads from natural products is the lack of effective tools to identify and separate the bioactive compounds. This project will develop and characterize a new magnetic separation approach based on cell membrane-encapsulated iron oxide superparticles (a cluster of nanoparticles) for the separation and identification of bioactive compounds from natural products. This method overcomes limitations of costly and time-intensive conventional approaches and the nonspecific binding problems of magnetic bead separation techniques. The new approach is also broadly applicable to many different types of transmembrane drug targets. The success of this project will advance industrial processes for identification and extraction of new drug leads from complex samples. The impact of this project will be further enhanced through student-led educational and outreach activities, including: (a) establishing a goal-oriented training mechanism and relevant course work for undergraduate researchers and (b) developing a STEM lead the way program with an emphasis on math concept building. Specific science outreach projects to be developed are Science middle school-targeted Olympiad training modules and magnetic fishing experiments for elementary school students through the "Science Party for Kids" program. The objective of this project is to develop a new magnetic separation approach based on cell membrane-encapsulated iron oxide superparticles (CSMPs) for the identification and separation of bioactive compounds from natural products. CSMPs will feature immobilized cell membranes with fully functional receptors that allow for identification of compounds specifically binding to the transmembrane receptors. The full encapsulation of magnetic superparticles inside a cell membrane overcomes the non-specific binding problems associated with the current magnetic bead separation technology. The use of magnetic superparticles enables rapid identification and extraction of compounds targeting transmembrane proteins. The CSMP approach is also easily translated to different transmembrane protein targets, which significantly broadens the applicability of this separation technique. Toward the overall objective, the PIs will develop, characterize, and evaluate the CSMP approach using cell membranes with functional nicotinic receptors to effectively identify binding compounds both in an artificial mixture (known binders and non-binders) and cigarette smoke condensates. The technique will be further verified using cell membranes with functional transient receptor potential (TRP) channels (e.g., TRPV1) and voltage-gated sodium channels. Both types of receptors have been shown as valid targets for the development of novel analgesic drugs. The outcome of the project will be fundamental knowledge related to efficient separation of bioactive compounds from complex matrices.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.