Multifunctional mesoporous silica nanospheres for biosensor, stimuli-responsive controlled-release drug delivery carriers and gene transfection vectors

Lai, Cheng-Yu
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Structurally well-defined mesoporous silica materials with tunable pore size and narrow pore-size distribution have attracted much attention for their potential applications in sensing, drug delivery and gene transfer. A series of mesoporous silica nanosphere-based (MSN) nano-devices were synthesized and utilized for the aforementioned applications.;For sensing application, we provide a first example in utilization of a multi-functionalized mesoporous silica material to selectively detect dopamine. A second application, rooted in this work, is the selective detection of amino-containing neurotransmitters under physiological condition.;The drug delivery applications have been built around a controlled release drug delivery device. In the original conception, the system is using surface-derivatized cadmium sulfide (CdS) nanocrystals as chemically removable caps to encapsulate several drug molecules and neurotransmitters inside the organically functionalized MSN mesoporous framework. To study the cap-dependence release profile, adenosine 5-triphosphate (ATP) molecules were encapsulated in the MSNs followed by capping of the mesopores with chemically removable caps, such as CdS nanoparticles and poly(amido amine) dendrimers (PAMAM). A luciferase chemiluminescence imaging method was employed to investigate the kinetics and mechanism of the ATP release with various disulfide-reducing agents as uncapping triggers in real time. By varying the chemical nature of the "cap" and "trigger" molecules in our MSN system, we observed that the release profiles could be regulated.;Further, the PAMAM dendrimers of low generations were utilized as MSN caps for drug delivery. The biocompatibility and delivery efficiency of the later MSN system in interaction with HeLa cervical cancer cells were demonstrated. The system renders the possibility to serve as a universal transmembrane carrier for intracellular drug delivery and imaging applications. This is the first uptake study of MCM-41 type mesoporous silicas into eukaryotic cells.;The last application presented in the current dissertation is gene delivery. A MSN based gene transfection system was developed, where second generation (G2) PAMAMs were covalently attached to the surface of MSN. The G2-PAMAM-capped MSN material (G2-MSN) was able to complex with a plasmid DNA (pEGFP-C1). The gene transfection efficacy, uptake mechanism, and biocompatibility of the G2-MSN system with various cell types were investigated.

Chemistry, Inorganic chemistry