A ZIF-90 nanoplatform loaded with an enzyme-responsive organic small-molecule probe for imaging the hypoxia status of tumor cells

Abstract

Hypoxia is one of the most common and important features occurring across a wide variety of malignancies, which can have adverse effects on the 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⁻¹) 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 a co-solvent. Inspired by the recent investigations on metal–organic frameworks (MOFs), a dual pH and ATP-responsive ZIF-90 nanoplatform was synthesized, and then PEG was post-modified through a Schiff base reaction. This allows the platform to serve as a carrier to load the hypoxia-responsive probe to investigate its response to enzyme in cells and in mice without using dimethyl sulfoxide as a co-solvent. Consequently, the two probes we synthesized here can successfully respond to nitroreductase for turn-on fluorescence imaging at a 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 the MOFs. Our results open up a promising way for the design and application of both enzyme-responsive probes and MOFs.