Cong Li from the Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, Shanghai 201203, China

Acidification of extracellular pH (pHe) is a universal characteristic of solid tumor regardless of their genotypes or phenotypes. The acidic pHe plays important role in tumor invasion, migration and metastasis by driving protease-mediated digestion, disrupting cell-matrix interaction and up-regulating the metastatic potential of cancer cells. Currently most fluorescence probes detected the neoplasia by targeting the tumor-associated receptors over-expressed on the cancer cell membrane.
However, the expression level of these receptors is hard to predict, which compromises imaging sensitivity and accuracy. Furthermore, the signal of the receptor-targeting probes always stays at a high level, which leads to a strong background signal in normal tissue due to non-specific binding. In this work, a novel biodegradable nanoprobe that showed pH-activated near-infrared (NIR) fluorescence was developed. This probe visualized both subcutaneous and orthotopic human glioblastoma U87MG xenografts with sensitivity and target to background ratio in vivo. Overall, the work provides a prototype to visualize the solid tumor in vivo with high sensitivity and minimal systemic toxicity by sensing the tumor acidic microenvironment.