Recent advances of novel targeted drug delivery systems based on natural medicine monomers against hepatocellular carcinoma.

Hepatocellular carcinoma (HCC), the most prevalent type of liver cancer, is often diagnosed at an advanced stage. Surgical interventions are often ineffective, leading HCC patients to rely on systemic chemotherapy. Unfortunately, commonly used chemotherapeutic drugs have limited efficacy and can adversely affect vital organs, causing significant physical and psychological distress for patients. Natural medicine monomers (NMMs) have shown promising efficacy and safety profiles in HCC treatment, garnering attention from researchers. In recent years, the development of novel targeted drug delivery systems (TDDS) combining NMMs with nanocarriers has emerged. These TDDS aim to concentrate drugs effectively in HCC cells by manipulating the characteristics of nanomedicines, leveraging receptor and ligand interactions, and utilizing endogenous stimulatory responses to promote specific nanomedicines distribution. This comprehensive review presents recent research on TDDS for HCC treatment using NMMs from three perspectives: passive TDDS, active TDDS, and stimuli-responsive drug delivery systems (SDDS). It consolidates the current state of research on TDDS for HCC treatment with NMMs and highlights the potential of these innovative approaches in improving treatment outcomes. Moreover, the review also identifies research gaps in the related fields to provide references for future targeted therapy research in HCC.