Multicomponent metal-organic framework nanocomposites for tumor-responsive synergistic therapy

• Published in: Journal of colloid and interface science 2023-09, Vol.645, p.663-675
• Main Authors: Hur, Won, Park, Yeongwon, Seo, Eunbi, Son, Seong Eun, Kim, Seongnyeon, Seo, Hyemyung, Seong, Gi Hun
• Format: Article
• Language: English
• Subjects: Cell Line, Tumor; Glucose Oxidase - chemistry; Humans; Hydrogen Peroxide - chemistry; Metal-organic framework; Metal-Organic Frameworks - chemistry; Nanocomposite; Nanocomposites; Nanoparticles - chemistry; Neoplasms - drug therapy; Neoplasms - pathology; pH-responsive; Reactive oxygen species; Synergistic therapy; Targeted tumor therapy; Tumor Microenvironment
• ISSN: 0021-9797; 1095-7103
• DOI: 10.1016/j.jcis.2023.04.161

[Display omitted] •Tumor microenvironment (TME)-activatable metal–organic frameworks (MOF) were developed for targeted tumor therapy.•pH-responsive breakdown of the framework gradually released glucose oxidase/Prussian Blue nanozyme, boosting tumor specificity.•Starvation therapy mediated by glucose oxidase was used to enhance chemodynamic therapy as well as to starve tumor cells.•Cascade catalytic reactions promoted ROS-induced DNA cleavage, growth inhibition, and finally tumor cell apoptosis.•The antitumor nanocomposites enabled chemodynamic/starvation synergism, high therapeutic efficiency, and minimal side effects. Targeted tumor therapy through tumor microenvironment (TME)-responsive nanoplatforms is an emerging treatment strategy used to enhance tumor-specificity to selectively kill cancer cells. Here, we introduce a nanosized zeolitic imidazolate framework-8 (ZIF-8) that simultaneously contains natural glucose oxidase (GOx) and Prussian blue nanoparticles (PBNPs) to construct multi-component metal-organic framework nanocomposites (denoted as ZIF@GOx@PBNPs), which possess cascade catalytic activity selectively within the TME. Once reaching a tumor site, GOx and PBNPs inside the nanocomposites are sequentially released and participate in the cascade catalytic reaction. In weak acidic TME, GOx, which effectively catalyzes the oxidation of intratumoral glucose to hydrogen peroxide (H2O2) and gluconic acid, not only initiates starvation therapy by cutting off the nutrition source for cancer cells but also produces the reactant for sequential Fenton reaction for chemodynamic therapy. Meanwhile, PBNPs, which are released from the ZIF-8 framework dissociated by acidified pH due to the produced gluconic acid, convert the generated H2O2 into harmful radicals to melanomas. In this way, the cascade catalytic reactions of ZIF@GOx@PBNPs enhance reactive oxygen species production and cause oxidative damage to DNA in cancer cells, resulting in remarkable inhibition of tumor growth. The tumor specificity is endowed by using the biomolecules overexpressed in TME as a “switch” to initiate the first catalytic reaction by GOx. Given the significant antitumor efficiency both in vitro and in vivo, ZIF@GOx@PBNPs could be applied as a promising therapeutic platform enabling starvation/chemodynamic synergism, high therapeutic efficiency, and minimal side effects.