Multifunctional iron-based Metal-Organic framework as biodegradable nanozyme for microwave enhancing dynamic therapy

Abstract

Nanozymes with excellent enzyme-mimicking catalytic property are playing an increasingly significant role in tumor diagnosis and therapy. Fe-metal organic framework nanoparticles (MIL-101(Fe) NPs) are prepared as nanozymes to generate reactive oxygen species (ROS) and induce cancer cell death by catalyzing endogenous substances in tumor microenvironment. Abundant stimuli-responsive hydroxyl radicals (·OH) are accelerated to generate in the presence of microwave irradiation, realizing microwave enhancing dynamic therapy (MEDT). Moreover, MIL-101(Fe) NPs possess biodegradability and bioresponsibility, which exhibit favourable properties of metabolism and non-toxic accumulation comparing with inorganic nanozymes. Fluorescent gold nanoclusters (BSA-Au NCs) are rapidly coupled with the surface of MIL-101(Fe) NPs to obtain MIL-101(Fe)@BSA-AuNCs NPs. MIL-101(Fe)@BSA-AuNCs NPs with magnetic resonance imaging (MRI) and fluorescent imaging (FI) not only image accurately for the site of tumor, but also monitor dynamic distribution process of MIL-101(Fe) in vivo. The signal intensity of FI and MRI reaches maximum at 1 h in the liver and 5 h in the tumor. Ionic liquid (IL) is also loaded into MIL-101(Fe)@BSA-AuNCs NPs as microwave sensitive reagents for microwave thermal therapy (MTT). This work synthesizes the nanozymes that possess degradability, microwave sensitivity and dual-mode imaging to achieve the combination of MTT and MEDT against tumor. Experiment result in vivo confirms that the kill rate of tumor is up to 96.65%, showing an outstanding anti-tumor efficacy.

Keywords: Cancer therapy; Enzyme mimics; Metal-organic framework; Microwave; Nanozyme.