Immunoregulatory activity and metal-ion-binding properties of a glycoprotein isolated from mountain cultivated ginseng.

This study investigates the immunomodulatory activities of a glycoprotein (MGP2) derived from mountain cultivated ginseng. Furthermore, it explores the binding properties of MGP2 with different metal ions, and develops a novel stimulus-responsive antitumor nano-platform (Cy@MGP2-Fe) based on the MGP2-cyclophosphamide‑iron complex. MGP2 enhances immunostimulation in RAW264.7 cells and splenocytes. It boosts phagocytosis and ROS production, and increases levels of NO, IL-6, and TNF-α in RAW264.7 cells. Moreover, it activates lymphocytes by promoting NO and TNF-α secretion. In addition, the immunostimulatory effect of MGP2 was assessed in C57BL/6 mice with cyclophosphamide-induced immunosuppression. The results showed that MGP2 could raise the spleen index and strengthen macrophage phagocytic ability. It also encouraged cytokine production in serum and splenic tissues. Furthermore, MGP2 can alleviate intestinal barrier damage in cyclophosphamide-induced mice, which may be attributed to enhancing the expression of tight junction proteins and regulating the composition of intestinal microbiota. MGP2 can form nanoparticles through complexation with various metal ions (K, Mg, Fe, and Zr). Moreover, a novel stimulus-responsive antitumor nanoplatform based on the MGP2-cyclophosphamide‑iron complex (Cy@MGP2-Fe) was successfully fabricated. This system integrates multiple therapeutic modalities, combining the immunostimulatory activity of the natural macromolecular glycoprotein (MGP2), the chemotherapeutic potential of cyclophosphamide (Cy), and the chemodynamic therapy (CDT) function of iron ions. This study demonstrates that MGP2 can alleviate cyclophosphamide-induced immunosuppression. Meanwhile, innovatively combining MGP2 with modern nanotechnology, a multifunctional nonsystem based on full-active pharmaceutical ingredients (full-API) has been constructed, which provides a highly promising strategy for enhancing efficacy and reducing toxicity in cancer therapy.