Multifunctional Mesoporous Silica Nanoparticles for Intracellular Controlled Release

该奖项在化学学部的无机、生物无机和有机金属化学项目和材料研究部门的生物材料项目中获得，支持爱荷华州立大学的Victor Lin教授合成具有生物相容性、多功能的介孔二氧化硅纳米颗粒（MSN）材料，这些材料具有良好的颗粒形态和可调的表面特性，可以有效地穿透不同的细胞膜。一系列的孔盖和解盖策略将被开发出来，这些策略可以由细胞化学物质和酶触发，用于研究动物和植物细胞内各种客体分子（如药物、显像剂、肽、蛋白质和核苷酸）的细胞内控制释放。具体目标是：1)合成生物相容性介孔二氧化硅纳米颗粒以控制膜运输，2)微调msn的表面特性以装载和释放化学物质，3)开发不同的孔盖和解盖策略，4)研究内吞作用，细胞内运输和控释机制。将在体外研究具有不同颗粒形态的多功能msn与动物和植物细胞之间的各种相互作用。这些相互作用包括：二氧化硅微球在细胞膜上的吸附，内化的机制和动力学，内化二氧化硅微球的细胞内定位，生物相容性，以及二氧化硅微球对细胞代谢的影响。将采用一系列成像、细胞化学和细胞分选技术来研究msn的细胞摄取动力学和细胞内从msn中释放生物活性分子的动力学。这项研究为化学家、生物学家和材料科学家研究活细胞内的化学性质和生物化学提供了新的纳米材料。跨学科的工作也将为从事该项目的学生提供宝贵的培训。其他更广泛的影响包括：为研究生和本科课程开发新的课程材料，并向当地小学和高中推广。

This award in the Inorganic, Bioinorganic and Organometallic Chemistry program in the Division of Chemistry and the Biomaterials program in the Division of Materials research supports Professor Victor Lin at Iowa State University to synthesize biocompatible, multi-functionalized mesoporous silica nanoparticle (MSN) materials with well-defined particle morphology and tunable surface properties for efficient penetration across different cell membranes. A series of pore-capping and uncapping strategies will be developed that can be triggered by cellular chemicals and enzymes for studying intracellular controlled release of a variety of guest molecules, such as drugs, imaging agents, peptides, proteins, and nucleotides, inside of animal and plant cells. The specific objectives are to: 1) Synthesize biocompatible mesoporous silica nanoparticles for controlling membrane trafficking, 2) Fine-tune surface properties of MSNs for loading and release of chemicals, 3) Develop an arsenal of different pore-capping and uncapping strategies, 4) Study mechanisms of endocytosis, intracellular transportation, and controlled release. Various interactions between the multifunctional MSNs with different particle morphologies and animal and plant cells will be studied in vitro. These interactions include: the adsorption of MSNs to cell membranes, the mechanism and kinetics of internalization, the intracellular localization of internalized MSN, the biocompatibility, and the effects of MSNs on cellular metabolism. A series of imaging, cytochemical, and cell sorting techniques will be employed to study the dynamics of cellular uptake of the MSNs and the kinetics of intracellular controlled release of biologically active molecules from MSNs. This research offers new nanomaterials for chemists, biologists, and material scientists to study the chemical nature and biochemistry inside living cells. The interdisciplinary work will also provide valuable training to the students working on this project. Other broader impacts include: The development of new curricular materials for graduate and undergraduate courses and outreach to local elementary and high schools.