Immunomodulatory and anti-ovarian cancer effects of novel astragalus polysaccharide micelles loaded with podophyllotoxin
Mo Liu, Zixu Zhang, Jiahua Wang, Ruibo Guo, Lu Zhang, Liang Kong, Yu Yang, Juan Zang, Yang Liu, Xuetao Li
Abstract
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-PEG 2000 -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.