Porous materials have garnered significant interest within scientific community
mainly because of the possibility of engineering their pores for selective applications.
Currently, much research has focused on improving the therapeutic indices of the active
pharmaceutical ingredients engineered with nanoparticles.
The main goal of this dissertation is to prepare targetable and biodegradable
silica/organosilica nanoparticles for biomedical applications with a special focus on
engineering particle pores.
Herein, the design of biodegradable silica-iron oxide hybrid nanovectors with large
mesopores for large protein delivery in cancer cells is described. The mesopores of the
nanomaterials span 20 to 60 nm in diameter, and post-functionalization allowed the
electrostatic immobilization of large proteins (e.g., mTFP-Ferritin, ~534 kDa). The
presence of iron oxide nanophases allowed for the rapid biodegradation of the carrier in
fetal bovine serum as well as magnetic responsiveness. The nanovectors released large
protein cargos in aqueous solution under acidic pH or magnetic stimuli. The delivery of
large proteins was then autonomously achieved in cancer cells via the silica-iron oxide
nanovectors, which is thus promising for biomedical applications.
Next, the influence of competing noncovalent interactions in the pore walls on the
biodegradation of organosilica frameworks for drug delivery applications is studied.
Enzymatically-degradable azo-bridged organosilica nanoparticles were prepared and
then loaded with the anticancer drug doxorubicin (DOX). Controllable drug release was
observed only upon the stimuli-mediated degradation of azo-bridged organosilica
nanoparticles in the presence of azoreductase enzyme triggers or under hypoxia
conditions. These results demonstrated that azo-bridged organosilica nanoparticles are
biocompatible, biodegradable drug carriers and that cell specificity can be achieved both
in vitro and in vivo. Overall, the results support the importance of studying self-assembly
patterns in hybrid frameworks to better engineer the next generation of dynamic or “soft”
|Date of Award||Nov 2018|
- Physical Science and Engineering
|Supervisor||Niveen Khashab (Supervisor)|