Genetically engineered bio-composite mediated dual-modality imaging-guided synergistic chemo-FUAS for tumor therapy

Focused ultrasound ablation surgery (FUAS) combined with bacterial synergistic therapy has significant potential in solid tumors, however, this combination therapy has been limited mainly due to its weak anti-tumor effects, single imaging modality, and exhibition of tumor recurrence. Herein, we aim to develop a novel multifunctional bio-composite comprising the coating of polydopamine (pDA) and doxorubicin (DOX) on the surface of genetically engineered bacteria (GVs-E. coli) for the ultrasound imaging (USI) and photoacoustic imaging (PAI)-guided synergistic chemo-FUAS therapy of tumor. The bio-composite preferentially colonize into hypoxic tumor tissues, the gas vesicles (GVs) expressed in GVs-E. coli can effectively synergize to FUAS through their cavitation effect and perform USI, and the pDA coating on the surface can produce a uniform PAI signal. Simultaneously, FUAS can trigger the controlled release of chemotherapy drug DOX. Our results confirmed that a combination of biotherapy synergistic chemo-FUAS therapy resulted in significant tumor inhibition and extended survival of 4T1 breast tumor model. This strategy has the potential to solve the inherent limitations of traditional FUAS treatments, while improving the therapeutic effect in conjunction with chemotherapy. It provides a new paradigm for image-guided, multi-level collaborative anti-cancer therapy.