Hsin-Yin Chuang, a doctoral candidate in chemical engineering, will defend their dissertation titled “Adaptable Upa-Mediated Dendrimer Gel Nanoparticles for Therapeutic and Diagnostic Applications in Cancer and Atherosclerosis” Their advisor, Dr. Hu Yang is an adjunct professor in chemical and biochemical engineering. The dissertation abstract is provided below.

This dissertation presents the development of adaptive urokinase-type plasminogen activator (uPA)-mediated dendrimer nanoparticles for targeted therapy and diagnosis of cancer and atherosclerosis. These diseases share common features of inflammation and dysregulated cell death, yet current treatments lack precision and early detection capability. In the first study, a dual-targeted dendrimer gel nanoparticle (GDP-uPA/GTI) was designed to target uPAR and ribonucleotide reductase R2 in triple-negative breast cancer (TNBC). GDP-uPA/GTI effectively suppressed R2, induced apoptosis, necrosis, and cell-cycle arrest, and reduced tumor growth without toxicity. The second study expands this strategy to atherosclerosis through a uPA-functionalized, rapamycin-loaded dendrimer nanoparticle (G5PM-uPA/RA). This platform accumulated in plaques of Ldlr−/−mice, suppressed pro-inflammatory cytokines, reduced apoptosis and necrotic core size, and increased fibrous cap thickness, leading to significant inflammation modulation and plaque stabilization. The third study further advances the system for multimodal diagnosis by developing an MRI/NIR dual-imaging dendrimer nanoparticle to enable real-time visualization of uPAR-rich atherosclerotic plaques. Collectively, these studies establish an adaptable uPA-mediated dendrimer platform capable of precise drug delivery and disease monitoring across oncology and cardiovascular applications, offering a clinically translatable strategy for precision nanomedicine.