Folic acid-modified antigen-trapping nanoprobes for developing in situ tumor vaccines to inhibit metastasis and recurrence of ovarian cancer

Abstract Tumor vaccines hold promise in inhibiting tumor metastasis and recurrence by stimulating the immune system to target and eliminate heterogeneous tumors. However, the development of optimal strategies for in situ tumor vaccines and the establishment of reliable methods to ensure their efficacy remain challenges. In this study, we engineered a folate-modified antigen-trapping nanoprobe (AGO@FA-lip). This nanoprobe initially acquires tumor antigens and double-stranded DNA (dsDNA) by inducing immunogenic cell death in tumor cells through the DNA-damaging agent oxaliplatin (OXA). Nano-aluminum hydroxide (nano-Al(OH) 3 ) effectively captures and aggregates the released antigens, facilitating their recognition and presentation by dendritic cells. The combination of exogenous cyclic GMP-AMP (cGAMP) and dsDNA synergistically amplifies the activation of STING signaling pathways, leading to a remodeling of the tumor immune microenvironment and an enhancement of the anti-tumor immune response. In ovarian tumor models, AGO@FA-lip-mediated chemoimmunotherapy significantly inhibited tumor growth, metastasis, and recurrence, ultimately prolonging survival in mice. Transcriptomic analysis revealed extensive immune activation, particularly in pathways associated with antigen processing and presentation, T cell differentiation, and TNF inflammatory signaling. The design concept of AGO@FA-lip provides a clinically scalable strategy for developing in situ tumor vaccines to inhibit the metastasis and recurrence of ovarian cancer. Graphical Abstract