Selenium-core nanozymes dynamically regulates Aβ & neuroinflammation circulation: Augmenting repair of nervous damage

The entangled dynamic circulation between β-amyloid (Aβ) and neuroinflammation is the main reason for the failure of monotherapy in Alzheimer's disease (AD) at present. Excessive reactive oxygen/nitrogen species (RONS) plays a crucial role in this cycle and is a key factor in the mutual promotion of Aβ aggregation and neuroinflammation. Herein, we reported a multifunctional selenium-polydopamine nanozyme ([email protected]@Bor) with broad-spectrum antioxidant activity, thereby blocking this vicious circulation. [email protected]@Bor could effectively protect normal cells from oxidative damage by scavenging RONS, and restore mitochondrial homeostasis. In addition, [email protected]@Bor could shift the balance of microglia activation from the pro-inflammatory M1 phenotype to anti-inflammatory M2 phenotype, and restore its phagocytic ability to Aβ and nerve repair function. Furthermore, [email protected]@Bor also had the potential to inhibit the accumulation of Aβ, prevent the re-triggering of neuroinflammation, and avoid the re-formation of the vicious circle. As a result, such nanozymes was able to modulate the neuroprotective function of microglia and astrocytes in a short time, ameliorate neuroinflammation, reduce Aβ burden, and ultimately save memory decline and cognitive impairment in APP/PS1 transgenic AD mice. These results indicate that the well-designed nanozymes has significant benefits compared to the conventional single-target agents in the treatment of AD.