Nanozymes-Engineered Metal–Organic Frameworks for Catalytic Cascades-Enhanced Synergistic Cancer Therapy

Abstract

The efficiency of chemical intercommunication between enzymes in natural networks can be significantly enhanced by the organized catalytic cascades. Nevertheless, the exploration of two-or-more-enzymes-engineered nanoreactors for catalytic cascades remains a great challenge in cancer therapy because of the inherent drawbacks of natural enzymes. Here, encouraged by the catalytic activity of the individual nanozyme for benefiting the treatment of solid tumors, we propose an organized in situ catalytic cascades-enhanced synergistic therapeutic strategy driven by dual-nanozymes-engineered porphyrin metal–organic frameworks (PCN). Precisely, catalase-mimicking platinum nanoparticles (Pt NPs) were sandwiched by PCN, followed by embedding glucose oxidase-mimicking ultrasmall gold nanoparticles (Au NPs) within the outer shell, and further coordination with folic acid (P@Pt@P–Au–FA). The Pt NPs effectively enabled tumor hypoxia relief by catalyzing the intratumoral H2O2 to O2 for (1) enhancing the O2-dependent photodynamic therapy and (2) subsequently accelerating the depletion of β-d-glucose by Au NPs for synergistic starving-like therapy with the self-produced H2O2 as the substrate for Pt NPs. Consequently, a remarkably strengthened antitumor efficiency with prevention of tumor recurrence and metastasis was achieved. This work highlights a rationally designed tumor microenvironment-specific nanoreactor for opening improved research in nanozymes and provides a means to design a catalytic cascade model for practical applications.

Porous Pt Nanospheres Incorporated with GOx to Enable Synergistic Oxygen‐Inductive Starvation/Electrodynamic Tumor Therapy

“…Compared with MnO 2 and CaO 2 compounds for O 2 generation, Pt possesses remarkably lower cytotoxicity and strong stability in a physiological environment. [ 19 ] It is thus expected that the combination of Pt nanoparticles and GOx may potentially serve as an alternative therapeutic platform for EDT/starvation synergistic treatment with capability of modulating hypoxic microenvironment.…”

Glutathione‐Depleting Nanoenzyme and Glucose Oxidase Combination for Hypoxia Modulation and Radiotherapy Enhancement

“…However, the catalytic activity of GOX also declined when the oxygen content decreased, which resulted in hypoxic TME in solid tumors. Some synergistic strategies were utilized to activate GOX via alleviating hypoxia [ 45 ] including incorporating O 2 ‐carrying NPs, [ 8 ] constructing cascade catalytic reaction to generate O 2 from H 2 O 2 [ 46–48 ] or combination therapy of photothermal therapy. [ 49 ] Ionizing radiation leads to the generation of reactive oxygen species (ROS), which causes oxidative stress and induces cell apoptosis.…”

In vivo real-time tracking of tumor-specific biocatalysis in cascade nanotheranostics enables synergistic cancer treatment

“…[10][11][12] Most of the reported GOD-based biocatalytic strategies have mainly focused on the entrapment of GOD with tumor-specic nanocarriers for prolonged blood circulation duration, increased stability, and improved tumor-targeting ability. [13][14][15][16][17][18][19][20][21] Despite their signicant advances, there remains a lack of desirable GOD-based design strategy to predict in vivo behaviors and regulate the therapeutic efficiency of GOD in clinical applications.…”