Apatinib-loaded silicate nanoparticles coated with macrophage membranes and PD-1 antibody for enhanced chemo-immunotherapy in ovarian cancer via VEGFR2 and PD-1 dual inhibition

Ovarian cancer remains one of the most challenging malignancies to treat due to its aggressive nature and resistance to conventional therapies. In this study, we developed a nanoparticle-based system (Apa@SiO₂@MP) that combines chemotherapy with immune checkpoint inhibition for enhanced treatment of ovarian cancer. The system consists of mesoporous silica nanoparticles (SiO₂ NPs) coated with macrophage membranes (MP) and functionalized with programmed death 1 (PD-1) antibody, designed to improve the delivery and targeting of apatinib, a tyrosine kinase inhibitor. The system demonstrated effective drug encapsulation, controlled release, and stability in physiological environments. In vitro assays revealed that Apa@SiO₂@MP had minimal cytotoxicity in normal cells but significantly reduced cell viability in ovarian cancer cells (SKOV-3), highlighting its cancer-targeting ability. Apatinib effectively inhibited VEGFR2 expression and induced reactive oxygen species (ROS) production, further promoting anti-cancer effects. In vivo, Apa@SiO₂@MP treatment led to enhanced tumor inhibition, as well as significant immune response activation, including increased CD4⁺ and CD8⁺ T cells and elevated IFN-γ levels. This study provides a promising multi-modal strategy for overcoming challenges in cancer therapy by integrating chemotherapy, immunotherapy, and targeted drug delivery, offering potential for improved treatment outcomes in ovarian cancer.