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

Abstract

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.

Label-Free Single-Cell SERS Detection and Fluorescence Imaging of Molecular Responses to Endoplasmic Reticulum Stress under Electrical Stimulation

“…As shown in Figure c,d, the expression levels of EpCAM at low voltage basically remain the same, whereas the expression of EpCAM was significantly upregulated after ES at 1.1 V. Notably, the expressions of two classical cadherins (E-cadherin and N-cadherin) were checked using immunofluorescence, as shown in Figure e, the results of which indicated the expression increase of E-cad and the downregulation of N-cad within HepG2 cells after ES under different voltages. Furthermore, as shown in Figure f, the ratios of E-cad to N-cad calculated were obviously increased with voltages boosted, which can contribute to inhibiting tumor cell migration during epithelial mesenchymal transition …”

“…Furthermore, as shown in Figure 6f, the ratios of E-cad to N-cad calculated were obviously increased with voltages boosted, which can contribute to inhibiting tumor cell migration during epithelial mesenchymal transition. 36 ■ CONCLUSIONS…”

State-of-the-Art and Development Trend of Interventional Ultrasound in China

“…This advancement propels the precision of interventional medicine to a new level. Domestic scholars have extensively attempted to construct multimodal and multifunctional ultrasound contrast agents using different materials [46][47][48][49][50][51][52][53][54][55]. Briefly introducing the research of several Chinese scholars, Li et al [47] designed a phase-shifted polyethylene glycol polylactic acid (PLGA) nanoparticle (PLGA-PEG-FA) modified with folic acid as a molecular probe for US imaging.…”

Ultrasound Molecular Imaging of Bladder Cancer via Extradomain B Fibronectin-Targeted Biosynthetic GVs

“…[5][6][7][8] Recently, the nanoscale biosynthetic gas vesicles (GVs) with 200 nm particle size from Halobacterium NRC-1 (Halo) have been demonstrated excellent ultrasound contrast signals in murine livers and stronger tumor penetration capability for tumors. 9,10 Structurally, GVs have a 2 nm protein shell with hydrophobic inner surfaces and hydrophilic outer surfaces. [11][12][13][14] This particular structure allows GVs to permit gas from the surrounding media into the vesicle.…”