Combining Cobalt Ferrite Nanozymes with a Natural Enzyme to Reshape the Tumor Microenvironment for Boosted Cascade Enzyme-Like Activities

Abstract

Nanozymes with the merits of effective enzyme-mimic activities, tunable catalytic properties, pH/temperature tolerance, and high stability have been consumingly researched for nanocatalytic therapy. Herein, the union nanozymes and a natural enzyme nanoplatform (DMSN@CoFe 2 O 4 /GOD-PCM) are elaborately designed by simply depositing an ultrasmall cobalt ferrite (CoFe 2 O 4 ) bimetallic oxide nanozyme and natural glucose oxidase (GOD) that are loaded into the aperture (∼12 nm) of dendritic mesoporous silica (DMSN) for near-infrared-II-enhanced tumor therapy. Upon irradiation, the hyperthermia generated by CoFe 2 O 4 nanozymes unlocks the "gate" of phase-change material (PCM) for releasing GOD, which reshapes the specific tumor microenvironment (TME) through the glucose metabolism pathway. The resulting strengthened acid condition and a considerable amount of H 2 O 2 efficiently initiate the cascade catalysis reactions. Moreover, highly toxic hydroxyl radicals are generated with a Co/Fe dual-cycle system of ultrasmall CoFe 2 O 4 nanozymes. The in situ glutathione consumption and hypoxia relief further amplify oxidative stress. In addition, chemotherapeutic effects due to the cytotoxicity of cobalt ions enhance the therapeutic performance. Collectively, this study provides a proof of concept for TME-reshaped natural and artificial nanozyme cascade catalysis for combined reactive oxygen species-based therapy and chemotherapy.

Nanotechnological strategies to increase the oxygen content of the tumor

“…The in vitro and in vivo results indicated that the IrRu-GOx@PEG NPs could effectively induce 4T1 cell apoptosis. In addition, a nanoplatform (DMSN@CoFe 2 O 4 /GOD-PCM) was designed for NIR II-enhanced tumor therapy by depositing ultrasmall cobalt ferrite (CoFe 2 O 4 ) and GOx into the pore size of dendritic mesoporous silica ( Chang et al, 2022 ) ( Figure 6B ). After laser irradiation, the high temperature generated by CoFe 2 O 4 melts the phase change material (PCM) to release GOx, remodelling the TME through the glucose metabolism pathway.…”

The rational design of nanozymes for imaging-monitored cancer therapy

“…Chang and coworkers developed a nano-platform DCGP (DMSN@CoFe 2 O 4 /GOD-PCM) with a combination of nanozyme and natural enzyme, which was realized by the deposition of ultrasmall CoFe 2 O 4 bimetallic oxide and glucose oxidase (GOD) into the large mesopores of dendritic mesoporous silica (DMSN). 52 The cascade catalysis reactions of the CoFe 2 O 4 nanozymes were TME-activated. GOD strengthened the weak acidity of the tumor area and produced more H 2 O 2 .…”

Amorphous Fe-Containing Phosphotungstates Featuring Efficient Peroxidase-like Activity at Neutral pH: Toward Portable Swabs for Pesticide Detection with Tandem Catalytic Amplification

“…As discussed in Figure 1G,H there are two redox couples (Fe 2+ /Fe 3+ and W 5+ /W 6+ ) in the prepared Fe-PTs, which can facilitate the regeneration of Fe 2+ by capturing electrons from the W 6+ species. 43,44 Moreover, the high surface electron density of polyoxotungstate clusters in Fe-PTs can also accelerate the reduction of Fe 3+ to Fe 2+ (Figure 2D). 45 The two pathways synergistically promote the decomposition of H 2 O 2 into hydroxyl radicals.…”