Fe(III)-Porphyrin Sonotheranostics: A Green Triple-Regulated ROS Generation Nanoplatform for Enhanced Cancer Imaging and Therapy

To address the urgent need for effective sonodynamic therapy (SDT), a facile and efficient strategy is developed for fabricating a new class of sonotheranostics. Herein, a Fe(III)-porphyrin nano-sonosensitizer is prepared by a one-step coordination synthesis, and then anchored with Bis(DPA-Zn)-RGD and manganese superoxide dismutase (SOD2) siRNA. Benefiting from the delicate interactions of the Fe(III)-coordinated nanoformulations, a highly potent sono/gene combinational therapy guided by fluorescence/magnetic resonance imaging is achieved. Importantly, this sonotheranostics significantly enhances the SDT effect of porphyrin through the cancer-targeted delivery capability and enhanced reactive oxygen species production via triple-regulated approaches, including down-regulation of SOD2, depletion of glutathione, and generation of Fenton reaction. This work opens up new perspectives for developing versatile sonotheranostics to overcome the clinical challenges of SDT.