pH Transistor Nanoprobe Advances Cancer Detection and Surgery

Cancer exhibits profound genetic and phenotypic differences, therefore broad yet cancer-specific detection of malignant tumors is challenging. Anatomy-based imaging modalities (e.g., CT, MRI) have good spatial resolution but provide little disease-specific information. 2-Deoxy-2-[18F]fluoroglucose positron emission tomography (FDG-PET) allows near universal tumor detection by leveraging altered tumor metabolism, but it is limited by low spatial resolution and high false positive rates. Here we report a near infrared fluorescent pH transistor nanoprobe targeting extracellular tumor acidosis from dysregulated pH that drives many invasive properties of cancer. The nanoprobes delineated tumors with high spatial resolution (<1 mm) for a broad range of in vivo tumor models using different clinical cameras. Our results show targeting tumor pH downstream from deregulated metabolism provides a broad strategy with improved cancer specificity which makes the nanoprobe a useful adjuvant method to reduce false rates after FDG-PET. To validate the ability of nanoprobes to provide real-time, highly sensitive and specific illumination of cancer, we performed tumor acidosis guided detection of occult disease as well as surgery and demonstrated significantly improved long-term survival benefit in head/neck and breast cancers. This binary nanotransistor design achieves digitization of an analog biologic signal (pH) for signal amplification and noise reduction that improves the accuracy of cancer detection, intraoperative tumor visualization, and imaging of therapeutic response while providing a powerful tool for understanding dysregulated pH and cellular energetics in cancer.