Preparation of Macrophage-Targeted Rh2-lips GPs and Evaluation of Their Anticancer Efficacy

Ginsenoside Rh2 exhibits significant anticancer activity; however, its clinical application remains limited owing to low bioavailability and the inability to achieve targeted delivery to tumor tissues. In the present study, Rh2-lips GPs, a yeast dextran microcapsules-based biomimetic delivery system, are successfully fabricated via a two-step process: first, Rh2 is embedded into cationic liposomes using the thin-film dispersion method, and subsequently, the resulting Rh2-loaded liposomes are loaded into yeast dextran microcapsules through self-deposition and electrostatic interactions. In vitro digestion simulation experiments reveal GPs can protect Rh2-loaded liposomes from degradation in the gastrointestinal tract. As compared to free C6 and C6-labeled Rh2-lips, C6-labeled Rh2-lips GPs are observed to exhibit significantly higher drug accumulation in macrophages in vitro. Following oral administration, ICG-labeled Rh2-lips GPs are found to target and accumulate in the tumor tissues of H22 tumor-bearing mouse models. Furthermore, in vivo studies demonstrated that, compared to free Rh2 and Rh2-lips, Rh2-lips GPs are found to significantly inhibit tumor growth, reverse the phenotype of tumor-associated macrophages(TAMs) from the M2 to M1 type, and upregulate the expression levels of the inflammatory factors (P<0.05) in vivo. Overall, Rh2-lips GPs have the potential to enhance the bioavailability of Rh2 and its active targeting to hepatic tumors.