Co–Ferrocene MOF/Glucose Oxidase as Cascade Nanozyme for Effective Tumor Therapy

Abstract

Chemodynamic therapy (CDT), enabling selective therapeutic effects and low side effect, attracts increasing attention in recent years. However, limited intracellular content of H 2 O 2 and acid at the tumor site restrains the lasting Fenton reaction and thus the anticancer efficacy of CDT. Herein, a nanoscale Co-ferrocene metal-organic framework (Co-Fc NMOF) with high Fenton activity is synthesized and combined with glucose oxidase (GOx) to construct a cascade enzymatic/Fenton catalytic platform (Co-Fc@GOx) for enhanced tumor treatment. In this system, Co-Fc NMOF not only acts as a versatile and effective delivery cargo of GOx molecules to modulate the reaction conditions, but also possesses excellent Fenton effect for the generation of highly toxic •OH. In the tumor microenvironment, GOx delivered by Co-Fc NMOF catalyzes endogenous glucose to gluconic acid and H 2 O 2 . The intracellular acidity and the on-site content of H 2 O 2 are consequently promoted, which in turn favors the Fenton reaction of Co-Fc NMOF and enhances the generation of reactive oxygen species (ROS). Both in vitro and in vivo results demonstrate that this cascade enzymatic/Fenton catalytic reaction triggered by Co-Fc@GOx nanozyme enables remarkable anticancer properties.

Intelligent Fe–Mn Layered Double Hydroxides Nanosheets Anchored with Upconversion Nanoparticles for Oxygen‐Elevated Synergetic Therapy and Bioimaging

“…The decomposed Fe 3+ could catalyze endogenous H 2 O 2 to O 2 for PDT of UCSP while simultaneously being reduced to Fe 2+ , and Fe 2+ will then continue to generate •OH by undergoing a Fenton reaction with H 2 O 2 . [64,65] Mn 2+/3+ could react with H 2 O 2 to form Mn 3+/4+ and •OH, [66,67] the above reactions together constitute the CDT. In this way, the high yield of generated 1 O 2 by UCSP and •OH could cause efficient cell apoptosis and necrosis.…”

Electrochemical Applications of Ferrocene‐Based Coordination Polymers

“…Reproduced from Ref. [198] with permission from Wiley-VCH. significantly hinder tumor progression and eliminate cancer cells by activating the intracellular cascade enzymatic/Fenton reactions.…”

“…As illustrated in Figure 25, when the CoÀ Fc NMOF was not loaded with GOx, the Fenton reaction occurred inside cells but was quenched because of the finite amounts of H 2 O 2 and H + . [198] According to many reports, the introduction of highly electroactive Fc into CPs not only provides CP frameworks with flexibility and structural impeccability but also makes them suitable for various electrochemical, environmental, medical, and biochemical applications. [198] However, researchers are still trying to expand the amazing properties of Fc-CPs to discover new, useful, and effective electrochemical applications.…”

“…[198] According to many reports, the introduction of highly electroactive Fc into CPs not only provides CP frameworks with flexibility and structural impeccability but also makes them suitable for various electrochemical, environmental, medical, and biochemical applications. [198] However, researchers are still trying to expand the amazing properties of Fc-CPs to discover new, useful, and effective electrochemical applications. Thus, further work in this field is expected to pave the way to the design of Fc-CPs with multitasking properties.…”

Recent Advances in Crosslinked Nanogel for Multimodal Imaging and Cancer Therapy

“…In contrast, chemodynamic therapy (CDT) which utilizes hydrogen peroxide (H 2 O 2 ) to generate cytotoxic ROS such as singlet oxygen ( 1 O 2 ) and the hydroxyl radical has gained increasing attention because of its high tumor specificity [ 87 ]. Until now, numerous nanomaterials such as MnO 2 nanosheet and metal-organic frameworks (MOFs) have been developed for CDT [ 88 , 89 ].…”