Endogenous Amplification of Apoptosis via p53 Regulation using a Cascade Nanocatalytic Medicine

undergo a cascade reaction with NO released from L-Arg, generating highly cytotoxic peroxynitrite (ONOO-), which has greater cytotoxicity to tumor cells, can induce extensive DNA damage, and simultaneously impair DNA repair and disrupt the cell cycle. Genome-wide RNA sequencing reveals MAL can activate the p53 pathway, thereby regulating apoptosis related proteins. In addition, MAL reduces mitochondrial membrane potential and promotes mitochondrial-mediated apoptosis through the BAX/Bcl-2/caspase-3 axis, further amplifying endogenous apoptosis in tumor cells. In vivo, MAL effectively inhibits tumor growth with favorable biocompatibility.