Chuanxiong Extract‐Decorated Mitochondria‐Targeted Nanocarriers Attenuate Infarct Injury by Restoring Mitochondrial Homeostasis and Blocking Oxidative Cascade

The complex phytochemical composition of Traditional Chinese Medicines (TCM) like Ligusticum chuanxiong offers multi-target therapeutic potential, yet their intracellular mechanisms remain largely undefined due to a lack of suitable investigative tools. We report a mitochondria-targeted nanoformulation (NSCE) created by loading Chuanxiong extract (CE) into amino-functionalized mesoporous silica nanoparticles (NS). We show that the adsorbed extract components unexpectedly confer mitochondrial tropism to the simple amino-functionalized silica nanoparticles, a function not inherent to the unmodified carrier. In vitro, NSCE selectively localizes to the mitochondria of cardiomyocyte, mitigating oxidative stress and dysfunction more effectively than free CE. In a rat model of ischemia/reperfusion injury, intramyocardial NSCE injection reduces infarct size and improves cardiac function. Mechanistically, NSCE synergistically modulates p53 and PI3K/AKT pathways to suppress apoptosis and oxidative stress, an action linked to its delivery of 52 identified bioactive constituents. This work introduces a paradigm where a complex herbal extract can functionalize a simple nanocarrier for organelle-specific delivery, offering a tractable strategy to dissect and harness the multitarget pharmacology of traditional medicines.