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

Area of Science:

• Biomedical Engineering
• Oncology
• Nanotechnology

Background:

• Focused ultrasound ablation surgery (FUAS) combined with bacterial therapy shows promise for solid tumors but faces limitations like weak efficacy and single imaging modalities.
• Tumor recurrence and suboptimal anti-tumor effects hinder the clinical translation of current combination therapies.

Purpose of the Study:

• To develop a multifunctional bio-composite for image-guided synergistic chemo-FUAS therapy.
• To engineer bacteria (GVs-E. coli) with polydopamine (pDA) and doxorubicin (DOX) for enhanced tumor treatment.

Main Methods:

• Genetically engineered E. coli (GVs-E. coli) were coated with pDA and DOX to form a bio-composite.
• Ultrasound imaging (USI) and photoacoustic imaging (PAI) were used for guidance.
• FUAS was employed to trigger DOX release and enhance therapy via bacterial gas vesicle cavitation.

Main Results:

• The bio-composite preferentially colonized hypoxic tumor tissues.
• Gas vesicles (GVs) from GVs-E. coli synergized with FUAS through cavitation, enabling USI.
• pDA coating provided a PAI signal, and FUAS triggered DOX release, leading to significant tumor inhibition and extended survival in a 4T1 breast cancer model.

Conclusions:

• The developed bio-composite offers a novel strategy for image-guided, multi-level synergistic cancer therapy.
• This approach addresses limitations of traditional FUAS and improves therapeutic outcomes when combined with chemotherapy.
• The strategy presents a new paradigm for collaborative anti-cancer treatments.