Biomimetic PD-1-nanovesicles inducing tri-modal sonodynamic-chemo-immunotherapy for breast cancer therapy and lung metastasis inhibition.

[BACKGROUND] Current cancer therapeutic approaches demonstrate constrained efficacy and fail to effectively address tumor metastasis, underscoring the critical need for innovative treatment modalities.

[RESULTS] In this study, we developed an innovative PD-1 cell membrane-coated nanoplatform (PD-1-Au@DOX) that integrates ultrasound (US)-responsive gold nanoparticles (AuNPs), doxorubicin (DOX) delivery, and PD-L1 blockade into a synergistic therapeutic system. In vitro studies demonstrate that PD-1-Au@DOX enables targeted delivery of DOX and AuNPs to PD-L1-expressing breast cancer cells (4T1 and MCF-7) via surface-bound PD-1, while concurrently blocking PD-L1 to initiate an immune response. Under US irradiation, AuNPs generate substantial reactive oxygen species (ROS), deplete intracellular glutathione, and increase DOX release. The synergistic interplay of these three pathways culminates in pronounced apoptosis in both 4T1 and MCF-7 cell lines. In murine breast cancer models, PD-1-Au@DOX + US demonstrated significant efficacy in primary tumor suppression, as evidenced by robust growth inhibition and prolonged survival. The coordinated activation of immune responses through PD-1/PD-L1 pathway modulation and US-mediated ferroptosis effectively suppressed lung metastasis.

[CONCLUSIONS] These findings establish PD-1-Au@DOX + US as a tri-modal approach for breast cancer treatment and metastasis prevention, providing an effective new clinical pathway.