Hepatic Stellate Cell‐Targeting Micelle Nanomedicine for Early Diagnosis and Treatment of Liver Fibrosis

Abstract Diagnosing and treating liver fibrosis is a challenging yet crucial endeavor due to its complex pathogenesis and risk of deteriorating into cirrhosis, liver failure, and even hepatic cancer. Herein, a silica cross‐linked micelles (SCLMs) based nano‐system is developed for both diagnosing and treating liver fibrosis. The SCLMs are first modified with peptide CTCE9908 (CT‐SCLMs) and can actively target CXCR4, which is overexpressed in activated hepatic stellate cells (HSCs). To enable diagnosis, an ONOO⁻‐responded near‐infrared fluorescent probe NOF2 is loaded into the CT‐SCLMs. This nano‐system can target the aHSCs and diagnose the liver fibrosis particularly in CCl₄‐induced liver damage, by monitoring the reactive nitrogen species. Furthermore, a step is taken toward treatment by co‐encapsulating two anti‐fibrosis drugs, silibinin and sorafenib, within the CT‐SCLMs. This combined approach results in a significant alleviation of liver injury. Symptoms associated with liver fibrosis, such as deposition of collagen, expression of hydroxyproline, and raised serological indicators show notable improvement. In summary, the CXCR4‐targeted nano‐system can serve as a promising theragnostic system of early warning and diagnosis for liver fibrosis, offering hope against progression of this serious liver condition.