Decomposable STING nanoagonist-amplified oncolytic virotherapy through remodeling the immunosuppressive microenvironment of triple-negative breast cancer.

Abstract

Oncolytic viruses (OVs) are promising for cancer treatment as they specifically replicate in tumor cells. However, the systemic delivery of OVs still faces the challenges of poor tumor targeting, short circulation periods, and limited lytic efficacy. Herein, an OV-concealed targeting nanoagonist (OV-MnO₂/HE) was prepared to enhance the delivery of OVs to triple-negative breast cancer (TNBC) via intravenous administration. Decomposable MnO₂ biomineral shells covered the surface antigens of OVs to prevent their clearance after systemic administration. The targeting materials of HA-EGCG (HE) enhanced intratumoral accumulation via active targeting. After entering tumors, OV-MnO₂/HE readily released Mn²⁺ and OVs, which could enhance the number of CD4⁺/CD8⁺ T cells and maturation dendritic cells (DCs) due to the synergetic effect of the STING pathway and OVs, thereby activating the immune response, resulting in the significant inhibition of TNBC growth. This work highlights the potential of the STING agonist in enhancing the antitumor efficacy of OVs and provides a potent platform for TNBC therapy.