Multiscale imaging on proton pump-driven acidity for assessing tumor progression and metastasis.

Area of Science:

• Biomedical Engineering
• Oncology
• Molecular Imaging

Background:

• The acidic tumor microenvironment (TME) is a key factor in cancer progression, invasion, and metastasis.
• Current methods for detecting and targeting tumor acidity lack sensitivity and specificity in vivo.
• ATP6V0C, a V-ATPase subunit, is identified as a critical mediator of TME acidification and is linked to hepatocellular carcinoma (HCC) progression.

Purpose of the Study:

• To develop a sensitive and specific method for real-time visualization and quantification of TME acidity.
• To investigate the role of ATP6V0C in HCC progression and metastasis.
• To explore the therapeutic potential of targeting tumor acidity.

Main Methods:

• Development of a pH-responsive ratiometric photoacoustic sensor (PPS).
• Utilizing PPS-assisted photoacoustic molecular imaging to monitor TME acidity during HCC development.
• Assessing the synergistic effect of PPS and esomeprazole on tumor growth suppression.

Main Results:

• High ATP6V0C expression correlates with increased HCC progression and metastasis.
• PPS successfully visualized the spatiotemporal evolution of TME acidity from early stages to solid tumors.
• PPS combined with esomeprazole demonstrated synergistic tumor growth suppression.

Conclusions:

• PPS-assisted photoacoustic molecular imaging offers a sensitive and specific approach for characterizing tumor initiation and progression.
• This technology has potential applications in early cancer diagnosis.
• Targeting the acidic TME with tools like PPS and proton pump inhibitors shows therapeutic promise.