Ultrasound-responsive biomimetic nanocarrier triggers spatiotemporal PROTAC release and ROS storm to disrupt TNBC immunosuppression via coordinated apoptosis/ferroptosis/senescence activation - PubMed
4 hours ago
- #Immunotherapy
- #Breast Cancer
- #Nanotechnology
- Development of a biomimetic nanocarrier (MTB@LM) targeting triple-negative breast cancer (TNBC) with BRD4-targeting PROTAC and sonosensitizers.
- Ultrasound activation triggers Mn-enhanced sonodynamic therapy (SDT) to amplify ROS and overcome hypoxia/GSH resistance.
- The nanocarrier induces coordinated apoptosis, ferroptosis, and senescence to promote immunogenic cell death (ICD).
- Senescent tumor cells are eliminated by αPD-L1 immunotherapy, blocking immune evasion.
- In orthotopic TNBC models, the treatment achieved >85% tumor suppression and remodeled the immunosuppressive microenvironment.
- Combination with αPD-L1 synergistically inhibited lung metastasis (>90%) and established durable immune memory.