Date of Award
Open Access Dissertation
College of Pharmacy
Nanoparticle-based targeted therapeutics have revolutionized the field of pharmaceutics by providing precise and efficient drug delivery systems. These therapeutics utilize nanoparticles as carriers to transport drugs selectively to the target site, reducing side effects and enhancing therapeutic efficacy. Although significant advancements have been made in nano-targeted therapies, there are many challenges that need to be addressed to fully realize their potential.
In this study, we proposed a novel approach to extend the potential application of anti-Programmed Death Ligand 1 (PD-L1) antibody (aPDL1) in cancer treatment and Alzheimer’s disease therapy by leveraging the Trim-Away pathway. aPDL1-based Trim-Away involves tagging target PD-L1 with TRIM21, and followed by proteasome-mediated degradation of PD-L1, leading to the suppression of immune checkpoints and enhanced immune activation.
By integrating nanotechnology with the Trim-Away pathway, we aim to overcome the current constraints for in vivo therapies and pave the way for a revolutionary era of targeted treatment. In order to harness the potential of the Trim-Away pathway, we developed a nanogel-facilitated protein intracellular specific degradation (Nano-ERASER) system to downregulate intracellular PD-L1. This groundbreaking development empowers us to selectively and efficiently administer aPDL1, achieving cancer targeted therapy in adult animals. Moreover, it even allows for the transportation of these agents across the blood-brain barrier, thereby facilitating treatments for central nervous system (CNS) diseases, including Alzheimer’s disease.
The convergence of nanotechnology and the Trim-Away pathway offers a unique therapeutic approach for selectively downregulating PD-L1 within living organisms. Further exploration and advancement in this realm will undoubtedly facilitate expanding aPDL1 applications in numerous diseases characterized by PD-L1 upregulation.
Wang, M.(2023). PD-L1 Nano-Eraser: A Novel Intracellular PD-L1 Degradation Approach and Its Application in Cancer and Alzheimer’s Disease Therapy. (Doctoral dissertation). Retrieved from https://scholarcommons.sc.edu/etd/7401
Available for download on Sunday, August 31, 2025