Title
Mesoporous silica nanoparticles as smart and safe devices for regulating blood biomolecule levels
Degree Type
Dissertation
Date of Award
2011
Degree Name
Doctor of Philosophy
Department
Chemistry
First Advisor
Victor S. Lin
Second Advisor
Brian G. Trewyn
Abstract
Stimuli-responsive end-capped MSN materials are promising drug carriers that securely deliver a large payload of drug molecules without degradation or premature release. A general review of the recent progress in this field is presented, including a summary of a series of hard and soft caps for drug encapsulation and a variety of internal and external stimuli for controlled release of different therapeutics, a discussion of the biocompatibility of MSN both in vitro and in vivo, and a description of the sophisticated stimuli-responsive systems with novel capping agents and controlled release mechanism.
The unique internal and external surfaces of MSN were utilized for the development of a glucose-responsive double delivery system end-capped with insulin. This unique system consists of functionalized MSNs capable of releasing insulin when the concentration of sugar in blood exceeds healthy levels. The insulin-free nanoparticles are then up taken by pancreatic cells, and release inside of them another biomolecule that stimulates the production of more insulin.
The in vivo application of this system for the treatment of diabetes requires further understanding on the biological behaviors of these nanoparticles in blood vessels. The research presented in this dissertation demonstrated the size and surface effects on the interaction of MSNs with red blood cell membranes, and discovered how the surface of the nanoparticles can be modified to improve their compatibility with red blood cells and avoid their dangerous side effects.
In order to optimize the properties of MSN for applying them as efficient intracellular drug carriers it is necessary to understand the factors that can regulate their internalization into and exocytosis out of the cells. The correlation between the particle morphology and aggregation of MSNs to the effectiveness of cellular uptake is discussed and compared with different cell lines. The differences in the degree of exocytosis of MSNs between healthy and cancer cells is reported and found to be responsible for the asymmetric transfer of the particles between both cell types.
The fundamental studies on the hemocompatibility, endo- and exocytosis of MSN along with its ability to sequentially release multiple therapeutics in response to different stimuli, allow us to propose MSN as an intravascular vehicle with a great potential for various biomedical applications.
DOI
https://doi.org/10.31274/etd-180810-2284
Copyright Owner
Yannan Zhao
Copyright Date
2011
Language
en
Date Available
2012-04-30
File Format
application/pdf
File Size
147 pages
Recommended Citation
Zhao, Yannan, "Mesoporous silica nanoparticles as smart and safe devices for regulating blood biomolecule levels" (2011). Graduate Theses and Dissertations. 12087.
https://lib.dr.iastate.edu/etd/12087