GSH‐Depleted Nanozymes with Dual‐Radicals Enzyme Activities for Tumor Synergic Therapy

Abstract

Although inspiring progress has been achieved in tumor nanocatalytic therapies based on tailor‐made nanozymes for converting hydrogen peroxide into reactive oxygen species (ROS) efficiently, most cytotoxic hydroxyl radicals do not spread far enough within a cell to damage the primary organelles for effective tumor therapy due to their short half‐life time (≈1 µs). Developing a novel nanocatalyst platform involving longer half‐life time ROS is desired. To this end, Fe3O4‐Schwertmannite nanocomposites (Fe3O4‐Sch) with triple‐effect tumor therapy are constructed through a facile method. The Schwertmannite shell converts the •OH produced by Fe3O4 via the Fenton reaction into sulfate radicals with a longer half‐life time (30 µs). Combination of dual radicals exhibits overwhelming tumor inhibition efficacy. The nanocomposites also show the multifunctionality of good photothermal efficiency (33.2%) and synergistic oxidative stress amplification upon glutathione biosynthesis (GSH) depletion by the l‐buthionine sulfoximine (BSO) molecules loaded in the hollow Fe3O4 cores. The comprehensive properties of the nanoplatform including the dual‐radical production, Fe3O4 nanocrystal mediated PTT, and the BSO mediated GSH depletion result in remarkable tumor inhibition both in vitro and in vivo, which may pave a way to constructing a synergic catalytic nanoplatform for efficient tumor therapy.

Fe3O4/Ag/Bi2MoO6 Photoactivatable Nanozyme for Self‐Replenishing and Sustainable Cascaded Nanocatalytic Cancer Therapy

“…Therefore, combination therapy involving additional therapeutics is necessary. [ 23–28 ] This however complicates fabrication, encapsulation, delivery, and release processes, making it not practical due to poor reproducibility, reduced effectiveness, high side‐effects, and high cost.…”

“…Therefore, combination therapy involving additional therapeutics is necessary. [23][24][25][26][27][28] This however complicates fabrication, encapsulation, delivery, and release processes, making it not practical Catalytic cancer therapy based on nanozymes has recently attracted much interest. However, the types of the current nanozymes are limited and their efficiency is usually compromised and not sustainable in the tumor microenvironment (TME).…”

Recent Trends in Composite Nanozymes and Their Pro-Oxidative Role in Therapeutics

“…However, the extremely short half-life (∼1 µs) of •OH restricts its future application. This problem was addressed by constructing Fe 3 O 4 nanocrystals coated with Schwertmannite (Sch) matrix (Sch@Fe 3 O 4 ), which possessed the ability to generate SO 4 • - radicals from SO 4 2- when attacked by •OH radicals in a cascade reaction ( Wu et al, 2021 ). Fe 3 O 4 hollow core generates •OH in Fenton’s reaction, which is converted to SO 4 •- (half-life of ∼30 µs) by nanoscale cellular pseudopodia-shaped Sch grown on the Fe 3 O 4 core.…”

A Potent Strategy of Combinational Blow Toward Enhanced Cancer Chemo‐Photodynamic Therapy via Sustainable GSH Elimination

“…This inhibition leads to a dilemma on the use of multimodal therapy, which has already demonstrated a superadditive effect for cancer treatment. [ 12–20 ] Currently, stunning GSH depletion strategies that are used in combination with cancer therapy are mainly focused on the direct elimination of GSH [ 4,21–28 ] or on the elimination of its upstream molecules, such as L‐cysteine, which are required for the synthesis of GSH. [ 1,29 ] Various enzyme inhibitors efficiently block the generation of intracellular GSH.…”

“…This inhibition leads to a dilemma on the use of multimodal therapy, which has already demonstrated a superadditive effect for cancer treatment. [12][13][14][15][16][17][18][19][20] Currently, stunning GSH depletion strategies that are used in combination with cancer therapy are mainly focused on the direct elimination of GSH [4,[21][22][23][24][25][26][27][28] or on the elimination of its upstream molecules, such as L-cysteine, which are required for the synthesis of GSH. [1,29] Various enzyme inhibitors efficiently block Excessive glutathione (GSH), which is produced owing to abnormal metabolism of tumor cells, scavenges photo-induced reactive oxygen species (ROS) and consumes chemotherapeutic drugs, thereby attenuating the efficacy of photodynamic therapy and chemotherapy, respectively.…”