Intratumoral therapeutic dust for chemo-photodynamic combination treatment

Implantable wireless ultrasound microdevices for intratumoral therapy are hindered by inadequate miniaturization for deep-seated sites and toxic lead-based piezoelectrics. Here, we report an injectable, lead-free, submillimeter therapeutic dust (TheraDust; 1.0 millimeters by 1.0 millimeters by 0.9 millimeters) for ultrasound-driven wireless chemo-photodynamic combined therapy. The core of the device is a lead-free tin-doped barium titanate piezoelectric ceramic that features a multiphase coexistence at physiological temperature and exhibits a high piezoelectric coefficient (d33 = 460 picocoulombs per newton). The TheraDust integrates with an ultrasound-responsive drug-loaded hydrogel for precise intratumoral injection. Under programmable ultrasound, it generates light for photodynamic therapy and triggers on-demand chemotherapeutic release for enhanced treatment. In animal models of breast cancer, the device achieved potent tumor suppression, reducing the final tumor volume to less than 3% after five treatment sessions (5 minutes each) and could be retrieved minimally invasively posttreatment. This platform can be adapted to deliver a range of therapeutic stimuli wirelessly, offering a versatile strategy for treating deep-seated pathologies.