Pharmaceutical Nanofactories: Intracellular synthesis of bioactive drug molecules

项目总结： 自从抗癌和化疗药物被发现以来，社会就受到了挑战 通过有害的和改变生命的副作用，通过细胞突变产生的耐药性，以及分布在非 新陈代谢的药物回到环境中，这对野生动物和 供水系统。我的团队对介孔二氧化硅孔环境的合成控制 纳米颗粒(MSN)提供了一种独特的视角，可以将活性、多相的催化物种输送到 细胞。利用已知的大量知识库，通过内吞作用将MSN内化为药物 交付，我们将设计生物兼容的多孔纳米材料，将进入细胞与无机和 生物催化剂被困在毛孔里。不具有生物活性的受保护分子将 一旦它们遇到催化活性部位就会被激活。提供的密闭空间 中孔将保护催化物种(系留分子催化剂和外源酶) 细胞的还原环境。我们可以选择性地对外部和内部的毛孔进行功能化 环境，使我们能够控制细胞内的内化和稳定以及催化 属性。目前输送生物活性分子的技术存在许多缺点。 这种特定部位的合成可以消除。科学创新包括系统调查 包埋金属催化剂和酶的新型多孔生物材料的合成和 前药物和前荧光团分子在细胞内的激活。假设是如果催化剂 可以在MSN的孔结构中被支撑和保护，并且纳米材料将被 被细胞内化，然后生物正交化学反应可以在细胞内进行 在现场生产具有生物活性的分子，消除了输送药物分子的需要 会产生有害的副作用并导致耐药性。 本课题的教学创新体现在合作研究和团队研究活动上。 通过PI让高中的参与者参与进来。学生将接受实操培训 大量最先进的仪器以及化学合成、表征和 生化技术。这项研究也将用于指导每周一次的本科生生物化学 实验室实验，重点研究生物分子与无机物质之间的重要相互作用 用于酶稳定的底物，并作为课堂课程的一部分。对…的影响 学生是合作工作的第一手经验，也是进入科学课程的基本技能 研究和理解，如适当控制、统计分析和 理工科所需的沟通技巧。

Project Summary: Since the discovery of anticancer and chemotherapeutic pharmaceuticals, society has been challenged by detrimental and life altering side effects, drug resistance via cellular mutations, and distributed non- metabolized pharmaceuticals back into the environment, which has long-term effects on wildlife and water supplies. The synthetic control my team has on the pore environment of mesoporous silica nanoparticles (MSN) offers a unique perspective of delivering active, heterogenous catalytic species to cells. Using the vast knowledge base already known on internalizing MSN via endocytosis for drug delivery, we will design biocompatible porous nanomaterials that will enter cells with inorganic and biological catalysts entrapped inside the pores. Protected molecules that are not biologically active will become activated once they encounter the catalytic active sites. The confined space offered by the mesopores will protect the catalytic species (tethered molecular catalysts and exogenous enzymes) from the reductive environment of the cells. We can selectively functionalize the external and internal pore environments, allowing us to control the internalization and stabilization intracellularly along with catalytic properties. Current technology to deliver biologically active molecules contains numerous disadvantages the site-specific synthesis could eliminate. The scientific innovation includes a systematic investigation of novel porous, biomaterials entrapping metal catalysts and enzymes to investigate the synthesis and activation of prodrug and profluorophore molecules intracellularly. The hypothesis is that if catalysts can be supported and protected in the pore structure of MSN and the nanomaterial will be internalized by cells, then bioorthogonal chemical reactions can be conducted intracellularly to produce biologically active molecules on site eliminating the need for delivery of drug molecules that have detrimental side effects and lead to resistance. The teaching innovation of this project is in the cooperative and team-oriented research activities involving participants from high school through the PI. Students will receive hands-on training on numerous state-of-the-art instrumentations along with chemical syntheses, characterization, and biochemical techniques. This research will also be used to guide weekly undergraduate biochemistry laboratory experiments, focused on important interactions between biomolecules and inorganic substrates for enzyme stabilization and as part of the curriculum in lecture courses. The impact to students is first-hand experience in working cooperatively and essential skills that go into scientific research and understanding, such as the importance of proper controls, statistical analysis, and communication skills that are required in science and engineering.