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.
In this final outcome report, the research activities led by the late Prof. Victor S.-Y. Lin and Adj. Prof. Brian Trewyn in the past 5 years are summarized. Through these research efforts, we successfully accomplished the main goal of this project: synthesize biocompatible, multi-functionalized mesoporous silica nanoparticle materials with well-defined particle morphology and study the intracellular controlled release events of a variety of guest molecules, such as drugs, imaging agents, peptides, proteins, and nucleotides, inside the engineered mesopores. Mesopores are pores in the size range of 2 nm – 50 nm, our materials had pores between 3 – 12 nm. These results were disseminated to the scientific community through 19 different peer-reviewed publications. We developed a series of multi-functionalized mesoporous silica nanoparticle (MSN) materials that are non-toxic, tunable in particle size and morphology, and offer some control in cellular membrane trafficking. These MSN materials could also play a key role in building novel systems for applications in several emerging research areas, such as controlled release drug/gene delivery and selective catalysis. One unforeseen challenge during this project was the untimely and sudden death of the PI, Prof. Victor S.-Y. Lin in the spring of 2010. However, during the subsequent two years after his death, seven graduate students completed their thesis research and graduated with PhDs. Some specific examples of what we accomplished inlcude: developing dual delivery systems that release both insulin and cAMP, the neurotransmitter that signals the production of insulin in pancreas cells, extensive research and findings on the interaction of porous particles with human red blood cells, and surface bound ligands that control interaction with cell surface integrins depending on their three-dimensional conformation. This is just a small sample of the research we accomplished during the lifetime of this project. Prof. Lin and Adj. Prof. Trewyn successfully educated and mentored a dozen PhD students that were either directly or indirectly related to this research. Each of these graduates are now currently employed in industrial jobs or at academic institutions as faculty or post-doctoral researchers. In addition to extensive research activities, the initial PI (Prof. Lin) was involved in developing new coursework where undergraduates early in their college career were exposed to nanotechnology in laboratory classes that it was not previously covered in. Both PIs contributed to give 33 seminars either at conferences or different departments to disseminate information. Finally, both PIs invited middle and high school into their laboratories to tour a research active facility and observe the synthesis of some nanomaterials.
