Photoacoustic Chemical Imaging of Tumor Microenvironment pH for Prediction of Chemotherapeutic Efficacy in Breast Cancer

An acidic microenvironment is a hallmark of solid tumors, which occurs due to cancer cells' preferential utilization of aerobic glycolysis. Both <i>in vitro</i> and <i>in vivo</i> studies provide evidence that clinicians can exploit this acidity by selecting drugs whose efficacy is particularly affected by the tumor microenvironment (TME). However, noninvasive measurement of tumor pH remains challenging. Photoacoustic chemical imaging enhanced by pH-sensitive nanoparticles as contrast agents is a promising technique to address this need. This imaging technique was employed to quantitatively monitor the TME pH in mice bearing patient-derived xenografts undergoing simultaneous alkalization treatment and chemotherapy. Compared to controls, in alkalinized tumors, paclitaxel chemotherapy significantly reduced tumor size, increased tumor necrosis, and reduced cancer cell proliferation as validated by histopathology and immunohistochemistry. Thus, photoacoustic chemical imaging of TME pH may provide significant predictive value and represents a promising noninvasive, reliable technology for realizing personalized cancer chemotherapy.