Ultrasound Molecular Imaging of Epithelial Mesenchymal Transition for Evaluating Tumor Metastatic Potential via Targeted Biosynthetic Gas Vesicles

Epithelial mesenchymal transition (EMT) of tumor cells is recognized as the main driver to promote metastasis. Extensive researches suggest that gradually decreased E-cadherin (E-cad) and increased N-cadherin (N-cad) exist in the tumor cells during the EMT process. However, there still lacks suitable imaging methods to monitor the status of EMT for evaluating tumor metastatic potentials. Herein, the E-cad-targeted and N-cad-targeted gas vesicles (GVs) are developed as the acoustic probes to monitor the EMT status in tumor. The resulting probes have ≈200 nm particle size and good tumor cell targeting performance. Upon systemic administration, E-cad-GVs and N-cad-GVs can traverse through blood vessels and bind to the tumor cells, producing strong contrast imaging signals in comparison with the nontargeted GVs. The contrast imaging signals correlate well with the expression levels of E-cad and N-cad and tumor metastatic ability. This study provides a new strategy to noninvasively monitor the EMT status and help to evaluate tumor metastatic potential in vivo.