DEVELOPMENT OF SILICA BASED NANOPARTICLES FOR MULTIMODAL THERAPEUTIC DELIVERY

Doctoral Candidate Name: Priya Vadarevu
Program: Nanoscale Science
Defense Date and Time: January 28, 2022 – 2:00 PM
Defense Location: Online
Committee chair’s Name: Dr. Juan Vivero-Escoto
Committee Members: Dr. Kirill Afonin, Dr. Jerry Troutman, Dr. Rchard Chi, Dr. Susan Trammell, Dr. Yuri Nesmelov
Abstract:

Chronic diseases like cancer are characterized by complex interactions between multiple pathways leading to treatment resistance and invasiveness. Repeated cycles of cytotoxic monotherapies are susceptible to drug resistance induced by the upregulation of cytoprotective genes. Some common mechanisms that promote sustenance of cancer include- hypoxia, antioxidant response, anti-apoptotic protein synthesis, angiogenesis, and metastatic potential. Combinations that rely on the administration of more than one drug, with independent mechanisms of action enhance treatment efficacy remarkably. Downregulation of survival mechanisms alongside administration of mainstay cytotoxic treatments is a promising strategy for combination therapy.
The spatiotemporal regulation required for co-delivery of multiple drugs can be afforded by nanoparticles. Application of nanoparticles for making stable formulations of hydrophobic drugs or for the protection of nucleic acid therapeutics against enzymatic degradation, has been previously demonstrated. In particular, silica nanoparticles (SiNP) can be synthesized with versatility to package therapeutic cargo by physical encapsulation, chemical conjugation, or electrostatic binding. The design, synthesis and characterization of mesoporous silica and hybrid organosilica nanoparticles comprising bimodal combinations of – small molecule drugs, photosensitizers (PS), or siRNA, are discussed in this thesis. In vitro behavior of the synthesized nanomedicines and the resulting drug-drug interactions are evaluated in cancer cell lines.