Immunomodulatory and suppressive effects of dual-function micelle targeting FSHR in ovarian cancer therapy

Ovarian cancer (OC) remains highly lethal, primarily due to late-stage diagnosis, peritoneal metastasis, high recurrence rates, and a tumor microenvironment (TME) that suppresses immune responses, limiting treatment efficacy. To address these challenges, this study developed a novel targeted nanoplatform, PPT/FSHB-PNP-SA, to target intraperitoneal OC cells and inhibit there growth. The system utilizes an amphiphilic polymer (PNP-SA) formed by the covalent coupling of bioactive ginseng polysaccharide (PNP) with stearic acid (SA). PNP-SA self-assemble into microspheres, encapsulating the podophyllotoxin (PPT), and is modified with DSPE-PEG 2000 -FSHB on its surface. DSPE-PEG 2000 -FSHB enables the micelles to specifically target OC cells expressing the follicle-stimulating hormone receptor (FSHR). The PPT/FSHB-PNP-SA system exhibits dual anti-tumor effects: (1) PPT directly induces cancer cell apoptosis; (2) The PNP shell actively remodels the immunosuppressive TME by inhibiting immunosuppressive pathways and promoting M1 macrophage polarization. This combined chemotherapy-immunotherapy strategy, which integrates targeted delivery with TME remodeling, offers a promising treatment option for recurrent/resistant OC.