In vivo fiber-optic fluorescent sensor for real-time pH monitoring of tumor microenvironment

Fluorescence-based in vivo monitoring of tumor microenvironment (TME) markers is of great utility in both clinical practice and scientific research for cancer. Unfortunately, limited light penetration depth, photobleaching, and systemic toxicity of indicators hinder the clinical translation of the fluorescent sensing method. Herein, we propose a plug-and-play in vivo TME marker sensor by combining fluorescence and fiber-optic sensing technology, which provides a pathway to overcome the above challenges. The pH-sensitive ratiometric fluorescent probes were hydrophobically modified, and physically entrapped along with the anti-bleaching agents on optical fiber surface by a sol–gel material. The resulting sensor has a high pH detection resolution of 0.0050, and a fast response time of 4 s while performing excellent reproducibility, reversibility, stability, and biocompatibility. In addition, the sensor can be accommodated to magnetic resonance imaging (MRI) to realize multimodality of sensing and imaging. The animal test results show that the developed sensor can not only reveal the spatial distribution of acidification of TME to achieve tumor edge identification but also monitor the pH dynamics in both short and long terms to evaluate the lesion recovery after treatment, enabling great promise for niching the gap of intra- and post-operative lesion monitoring in tumor treatment.