Immunomodulatory and anti-ovarian cancer effects of novel astragalus polysaccharide micelles loaded with podophyllotoxin

Ovarian cancer, a highly lethal form of gynecological cancer globally, has witnessed notable advancements in its treatment through the integration of nanotechnology and immunotherapy. Here, we designed a novel astragalus polysaccharide vector (PDA), encapsulating podophyllotoxin (PPT), and modifying methotrexate (DSPE-PEG₂₀₀₀-MTX) on its surface for targeting ovarian cancer cells with high folate receptor expression. We prepared novel MTX-modified PPT-loaded astragalus polysaccharide micelles (MTX-PPT-micelles) by dialysis method and evaluated their characterization, stability, safety and targeting ability. EDU proliferation, apoptosis, wound healing, and macrophage polarization experiments were performed, and a mouse ectopic tumor model and a lung metastasis model were established to evaluate the antitumor effects of MTX-PPT-micelles. The prepared MTX-PPT-micelles had appropriate particle size, good stability and safety, and were able to achieve slow drug release. In vitro and in vivo experiments showed that MTX-PPT-micelles significantly enhanced tumor uptake and apoptosis, and significantly inhibited tumor proliferation, invasion and metastasis processes. In addition, MTX-PPT-micelles could improve tumor immunosuppression by shifting tumor-associated macrophages from M2 to M1 phenotype. In conclusion, this study successfully constructed a novel nano-delivery system to achieve targeted therapy for ovarian cancer by combating tumor cells with immunomodulatory effects on tumor-associated macrophages.