Over 1 million cancer surgeries are performed in the US and 5 million worldwide each year. Obtaining tumor-free surgical margins is important to achieve disease-free survival while minimizing removal of normal tissues is equally important to preserve quality of life. To achieve clear margin delineation in a broad set of tumors with diverse tissue origin and cancer genotypes/phenotypes, we have developed a transistor-like pH threshold sensor to image tumor acidosis, a universal cancer hallmark downstream of deregulated energetics (e.g., Warburg effect). HomoFRET-induced fluorescence quenching was employed at the micelle state to abolish fluorescent signals during blood circulation, but allow exponential activation in the mildly acidic tumor microenvironment. The signal amplification strategy allowed the detection of occult tumor nodules <1 mm in size. Real-time, fluorescence-guided surgery achieved >70% cancer cures in mice bearing head and neck tumors. Recently completed Phase 1 trial demonstrated the safety and effectiveness of the UPS nanosensor (ONM-100) in tumor detection, which led to a fast track status for a multi-centered Phase 2 trial by the FDA.
- Wang Y, Zhou K, Huang G, Hensley C, Huang X, Ma X, Zhao T, Sumer BD, DeBerardinis RJ, Gao J. A Nanoparticle-based Strategy for the Imaging of a Broad Range of Tumours by Nonlinear Amplification of Microenvironment Signals. Nat. Mater. 2014, 13, 204-212. PDF
- Zhao T, Huang G,Yang S, Ramezani, S, Li Y, Wang Y, Ma X, Xie XJ, Thibodeaux J, Sun X, Sumer BD, Gao J. A Transistor-like pH Nanoprobe for Tumour Detection and Image-Guided Surgery. Nature Biomed. Eng. 2016, 1, 0006. (Featured by Science daily news, Dallas Morning News, NBC5 and CBS11) PDF
- Huang G, Zhao T, Wang C, Nham K, Xiong Y, Gao X, Wang Y, Hao G, Ge WP, Sun XK, Sumer BD, Gao J. PET Imaging of Occult Tumours by Temporal Integration of Tumour-Acidosis Signals. Nature Biomed. Eng. 2020, 4, 314. PDF
- Bennett ZT, Feng Q, Bishop JA, Huang G, Sumer BD, Gao J. Detection of Lymph Node Metastases by Ultra-pH-Sensitive Polymeric Nanoparticles. Theranostics. 2020, 10(7), 3340-3350. PDF
- Voskuil FJ, Steinkamp PJ, Zhao T, van der Begt B, Koller M, Doff JJ, Jayalakshmi Y, Hartung JP, Gao J, Sumer BD, Witjes MJH, van Dam GM. Exploiting metabolic acidosis in solid cancers using a tumor- agnostic pH-activatable nanoprobe for fluorescence-guided surgery. Nature Comm. 2020, 11, 3257. PDF