Design and Synthesis of Porous Smart Materials for Biomedical Applications

Abstract

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” porous materials.