Abstract

Cancer-specific imaging remains a paramount challenge despite promise in early diagnosis, post-therapy monitoring as well as image-guided therapy of tumors. Achieving a broad and yet tumor-specific imaging efficacy presents a dilemma since conventional targeting of specialized cancer cell biomarkers (e.g. Her2/neu) often limits the outcome to a small subset of tumors. In this study, a more generalized strategy will be presented to achieve tumor-specific imaging by targeting universal tumor microenvironmental signals, namely the acidic extracellular pH (pHe) of tumors. This is accomplished by the development of ultra-pH sensitive (UPS) fluorescent nanoprobes, which can be turned ON/OFF within 0.20 pH unit with a large fluorescence activation ratio (>100-fold). These nanoprobes stay silent during blood circulation, but become activated inside tumors through non-linear amplification of tumor microenvironment signals. Broad tumor specificity was observed in various animal tumor models of diverse cancer genotypes. This nanoplatform opens up opportunities for image-guided surgery of tumors to improve resection accuracy.

© 2014 Optical Society of America