Effects of nanodelivery system PQR NPs on gene expression regulation in antagonizing erastin-induced PC12 cell damage via ferroptosis

In this report, we demonstrate that quercetin-loaded PQR NPs serve as a key regulatory vehicle in counteracting Erastin-induced damage to PC12 cells. The absence of PQR NPs markedly heightens PC12 cells' susceptibility to Erastin-induced ferroptosis, a phenomenon reversible through exogenous administration of PQR NPs.

Furthermore, PQR NPs interact both physically and functionally with core ferroptosis pathway genes (such as GPX4) and epigenetic modifiers, thereby regulating the expression levels of ferroptosis-related genes during Erastin-induced injury. Although PQR NPs are not essential for the transcriptional activity of core genes themselves, the quercetin delivery and release process mediated by PQR NPs is indispensable for scavenging excess reactive oxygen species within cells, maintaining GPX4 expression stability, and inhibiting Erastin-induced lipid peroxidation.