Vidit Singh, a doctoral candidate in chemical engineering, will defend their dissertation titled “Lipid Based Nanoparticles for Gene and Drug Delivery in Inflammatory Diseases.” Their advisor, Dr. Hu Yang, is Linda & Bipin Doshi Department Chair & Professor of Chemical & Biochemical Engineering. The dissertation abstract is provided below.

This thesis explores lipid-based nanocarriers for targeted and non-targeted delivery of nucleic acids and hydrophobic drugs in inflammatory diseases like cancer and cardiovascular disease models. In the first project, cationic liposomes encapsulating the TLR3 agonist Poly I:C were developed for immunotherapy in head and neck squamous cell carcinoma. These liposomes enhanced cytoplasmic delivery, activated innate immune signaling, and induced tumor regression in xenograft models.

The second project focused on liposomal encapsulation of ML-098, a hydrophobic RAB7 GTPase activator, for pulmonary arterial hypertension (PAH). Using a DMSO-assisted microfluidic method, ML-098 liposomes demonstrated 80% encapsulation, selective endothelial uptake, and therapeutic efficacy in a rat Hx/Su model at significantly reduced dosing compared to free drug. The final project centered on Hemo-LNPs, a novel mRNA delivery system for acute myeloid leukemia (AML). Formulated via a custom Dual Inlet Vortex Jet Mixer and optimized through Taguchi DOE, Hemo-LNPs achieved up to 99% transfection efficiency in AML cells. Delivery of TP53 and DNMT3L mRNAs resulted in functional protein expression and reduced leukemic proliferation, outperforming commercial LNPs.

Together, these studies demonstrate the therapeutic potential of tailored lipid nanocarriers for gene and drug delivery across diverse disease models.