Bacterial membrane-modified cerium oxide nanoboosters enhance systemic antitumor effects of radiotherapy in metastatic triple-negative breast cancer.

Abstract

Background: Radiotherapy plays an important role in the treatment of triple-negative breast cancer, yet its ability to trigger systemic responses against distant tumors remains limited.

Results: To address this challenge, we developed a biomimetic nanobooster by incorporating cerium oxide (CeO₂) nanoparticles with bacterial outer membrane vesicles (OMVs), termed CeO₂@OMV. This innovative strategy overcomes the limitations of conventional radiotherapy by enhancing antigen release and improving immune cell infiltration, thereby amplifying its effectiveness in combating both primary and metastatic tumors. The biocompatibility, antitumor effects, bystander and immunomodulatory impacts of the nanoboosters were assessed by comprehensive in vitro assays and in vivo breast cancer models. Our results demonstrated that CeO₂@OMVs can selectively inhibit cancer cells while protecting normal tissue upon irradiation. Additionally, the nanoboosters induced immunogenic cell death, enhanced macrophage polarization, and suppressed the growth of bystander tumors. In vivo studies demonstrated that CeO₂@OMVs, when combined with radiotherapy, significantly improved local tumor control and triggered systemic immune responses, leading to substantial inhibition of both primary and distant tumors, effectively preventing new metastases.

Conclusions: In conclusion, our CeO₂@OMV nanoboosters offer a promising therapeutic strategy against metastatic breast cancer, providing a novel tool to achieve radiation-induced abscopal effects.