Bioactive Ceria Nanoenzymes Target Mitochondria in Reperfusion Injury to Treat Ischemic Stroke

Abstract

Overproduction of reactive oxygen species by damaged mitochondria after ischemia is a key factor in the subsequent cascade of damage. Delivery of therapeutic agents to the mitochondria of damaged neurons in the brain is a potentially promising targeted therapeutic strategy for the treatment of ischemic stroke. In this study, we developed a ceria nanoenzymes synergistic drug-carrying nanosystem targeting mitochondria to address multiple factors of ischemic stroke. Each component of this nanosystem works individually as well as synergistically, resulting in a comprehensive therapy. Alleviation of oxidative stress and modulation of the mitochondrial microenvironment into a favorable state for ischemic tolerance are combined to restore the ischemic microenvironment by bridging mitochondrial and multiple injuries. This work also revealed the detailed mechanisms by which the proposed nanodelivery system protects the brain, which represents a paradigm shift in ischemic stroke treatment.

Advanced Nano-Drug Delivery Systems in the Treatment of Ischemic Stroke

“…Moreover, due to its peroxidase-like properties, ZIF-8 enhances the free radical scavenging ability of CeO 2 @ZIF-8 compared to free CeO 2 , showing excellent preventive and therapeutic effects in neuroprotective therapy for ISs. Liao et al introduced the concept of mitochondrial microenvironmental regulation and developed an NDDS based on CeO 2targeting mitochondria [162] (Figure 3). Mitigating oxidative stress injury can be achieved by regulating the mitochondrial microenvironment to promote ischemic recovery.…”