CART and Ceria nanozyme co-loaded ROS-responsive nanogel for synergistic treatment of Alzheimer's disease

Alzheimer's disease (AD) has displayed complex pathological features, in which oxidative stress and ferroptosis play important roles. The development of collaborative treatment methods aimed at multiple pathological factors is particularly important for effective alleviation of AD. In our research, a multifunctional delivery system (CART-CeO 2 )@HA was developed for the co-delivery of neuroprotective Cocaine- and amphetamine-regulated transcript (CART) peptides and antioxidant CeO 2 nanozymes encapsulated within an ROS-responsive nanogel. Under the stimulation of Aβ, (CART-CeO 2 )@HA exhibited effective relief for cell apoptosis, mitochondrial dysfunction and synaptic loss on account of ROS removal and ferrous ions chelation. With sufficient accumulation and sustained drug release in the brain of APP/PS1 mice, (CART-CeO 2 )@HA significantly reduced the levels of oxidative stress and ferroptosis, which facilitate the reduction of Aβ deposition and the repair of neuronal damage, jointly rescuing the cognitive impairment in APP/PS1 mice. These results verified the clinical potential of the multi-target delivery system in AD synergistic therapy.