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

ABSTRACT

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.