On November 7th, 2024, Nasir Arafath successfully defended his doctoral thesis titled “Functionalization and Evaluation of Antioxidant Cerium Oxide Nanoparticles (CNP) for Stroke Treatment.”
Stroke remains one of the leading causes of mortality and acquired disability globally, with ischemic stroke accounting for 87% of all cases. This condition arises from a blockage in a cerebral artery, typically caused by a thrombus. The only FDA-approved pharmacological treatment, recombinant tissue plasminogen activator (rtPA), works by dissolving thrombi but often has limited success. Recent research suggests that neutrophil extracellular traps (NETs), composed of DNA backbones, contribute to thrombus resistance against rtPA.
Additionally, the reperfusion following ischemic stroke generates excessive reactive oxygen species (ROS), which cause vascular damage and increase the risk of cerebral hemorrhage. Antioxidant therapies are, therefore, crucial for mitigating these effects. Cerium oxide nanoparticles (CNPs) are a promising therapeutic option due to their catalytic ability to neutralize ROS.
My research focused on developing a dual-function adjuvant therapy to enhance rtPA thrombolysis by combining the antioxidant activity of CNPs with the NET-degrading ability of DNase. However, bare CNPs face challenges such as aggregation at physiological pH, which limits their therapeutic applications.
In this thesis, I proposed and demonstrated two strategies to minimize CNP aggregation:
- Polymer Coating
- Lipid Coating
Furthermore, DNase enzymes were covalently grafted onto the coated CNPs to create dual-functional nanoparticles. The engineered nanoparticles were extensively characterized for their physicochemical properties, toxicity, cellular internalization, antioxidant activity, and DNA-degrading capabilities, highlighting their potential as an adjuvant therapy for ischemic stroke treatment.
This work provides a novel approach to overcoming key limitations in stroke treatment, paving the way for more effective therapeutic options
