Precision Visualization of Tumor Microenvironment via a Lysosome-Anchored Molecular Rotor with Viscosity-Triggered...

Intracellular viscosity is a key biomarker of the tumor microenvironment. However, most existing probes lacked tumor-targeting capabilities, limiting the accuracy of tumor detection and imaging analysis. Herein, we present a new fluorescent probe (NM-Lys), engineered for the highly selective and sensitive sensing of intracellular viscosity. Operating through a restricted intramolecular motion mechanism, NM-Lys exhibited a remarkable fluorescence enhancement (up to 21-fold) at 645 nm in high-viscosity environments. NM-Lys demonstrated outstanding selectivity for viscosity against potential interferents. Furthermore, NM-Lys could target the lysosomes and monitor the dynamic changes in lysosomal viscosity under oleic acid stimulation. Finally, by encapsulating NM-Lys into folic acid-functionalized liposomes, we designed a folic acid receptor-targeted nanoprobe (Lip-NM-FA), which ultimately facilitated the high-contrast visualization of tumor boundaries in a xenograft mouse model. This formulation achieved high-contrast fluorescence imaging of tumors in living mice by specifically targeting the high-viscosity microenvironment of tumor tissues. This research established NM-Lys as a robust analytical tool for monitoring tumors.