A ZIF-90 Nanoplatform Loading with Enzyme-Responsive Organic Small Molecule Probe for Imaging Hypoxia Status of Tumor Cells

Hypoxia is one of the most common and important features occurring across a wide variety of malignancies, which can cause adverse therapeutic outcomes of chemotherapy and radiotherapy. Therefore, the characterization of tumor hypoxia is of great importance in clinical tumor treatment. Herein, we firstly develop a new spectroscopic off−on probe with high sensitivity (detection limit: 5.8 ng/mL) and good selectivity for fluorescence imaging the hypoxic status of tumor cells via its enzymatic reaction with nitroreductase in vitro and in vivo in the presence of dimethyl sulfoxide (DMSO) as co-solvent. Inspired by the recent investigations on metal-organic frameworks (MOFs), a dual pH and ATP responsive ZIF-90 nano-platform was synthesized, and then PEG was post-modified through Schiff base reaction. This allows the platform as a carrier to load hypoxia-responsive probe to investigate its response to enzyme in cell and in mice without using dimethyl sulfoxide as co-solvent. Consequently, the two probes we synthesized here can successfully respond to nitroreductase for turn-on fluorescence imaging in cellular level and in tumor-bearing mice. This is the first time that an enzyme-responsive organic small molecule probe has been mounted on one of MOFs. Our results open up a promising way for the design and application of both enzymatic response probes and MOFs.