New horizons for the therapeutic application of nanozymes in cancer treatment

Abstract

The advent of nanozymes has revolutionized approaches to cancer diagnosis and therapy, introducing innovative strategies that address the limitations of conventional treatments. Nanozyme nanostructures with enzyme-mimicking catalytic abilities exhibit exceptional stability, biocompatibility, and customizable functions, positioning them as promising tools for cancer theranostics. By emulating natural enzyme reactions, nanozymes can selectively target and eradicate cancer cells, minimizing harm to adjacent healthy tissues. Nanozymes can also be functionalized with specific targeting ligands, allowing for the precise delivery and regulated release of therapeutic agents, improving treatment effectiveness and reducing adverse effects. However, issues such as biocompatibility, selectivity, and regulatory compliance remain critical challenges for the clinical application of nanozymes. This review provides an overview of nanozymes, highlighting their unique properties, various classifications, catalytic activities, and diverse applications in cancer treatments. The strategic oncological deployment of nanozymes could profoundly impact future advancements in personalized medicine, highlighting recent progress and prospective directions in enzyme-mimetic approaches for cancer treatment. This review summarizes an overview of nanozymes, highlighting their unique properties, various classifications, catalytic activities, and diverse applications in cancer treatments.

Keywords: Nanomaterials; Reactive-oxygen species; Therapy.

Fig. 1

Comparison of natural enzymes and nanozymes. Whereas HRP-Horseradish peroxidase, CQDs-Carbon quantum dots

Fig. 2

Chronological overview of key milestones in the historical progression of nanozyme research, focusing on atomic site innovations and catalytic therapeutic applications. Reproduced with permission from [32]

Fig. 3

Overview of nanozyme discovery, properties, classification, and therapeutic applications

Fig. 4

Classification of nanozymes: a comprehensive overview based on properties and functions [20]

Fig. 5

Schematic representation showing the catalytic reactions of different oxidoreductases and their mimics, including OXD, POD, SOD, and CAT

Fig. 6

Application of nanozyme in cancer therapy

Fig. 7

A Mechanism of NIR photothermal therapy. B Schematic illustration of the COF-derived N-doped carbon nanozyme with multiple enzyme-like activities and its anticancer mechanism, reprinted with permission from [103]. Copyright 2023, American Chemical Society. C Schematic illustration of PtSn BNCs for the phototheranostic effect and photothermal-enhanced catalytic therapy. Reprinted with permission from [104]. Copyright 2023, American Chemical Society. D Jablonski diagram illustrating the mechanism of photodynamic therapy (PDT). E Schematic diagram illustrating the synthesis of MMSC and its mechanism to amplify ferroptosis via MET inhibition and photodynamic therapy, reprinted with permission from [117]. Copyright 2024, Elsevier Ltd. F (a) Schematic illustration of synthesis tactics for Fe-TCPP-R848-PEG (Fe-MOF-RP) and (b) mechanism of light-driven nanozymes against tumor therapy reprinted with permission from [118]. Copyright 2023, American Chemical Society

Fig. 8

A Possible mechanism of sonodynamic therapy (SDT). B Schematic illustration of self-cascading MNZs with dual enzymatic GSH-OXD-like and POD-like activities for tumor-specific CDT, reprinted with permission [123]. Copyright 2024, Elsevier Ltd. C Schematic illustration of H₂O₂ self-suppling synergistic energy metabolism interference enhanced catalytic therapy, reprinted with permission [124]. Copyright 2024, Wiley–VCH GmBH. D Schematic diagram of potential mechanisms of SDT, reprinted with permission [135]. Copyright 2024, Wiley–VCH GmBH. E Schematic diagram for preparing the PdCu_x@LDH allays nanozymes and the proposed antitumor mechanism, reprinted with permission from [133]. Copyright 2024, American Chemical Society. F Schematic representation of the (a) synthesis of the PFMP nanozyme and (b) tumor accumulation and tumor microenvironment-responsive enhanced SDT mechanism, reprinted with permission from [134]. Copyright 2024, American Chemical Society

Fig. 9

A Schematic illustration of the mechanism of cancer immunotherapy, reprinted with permission [147]. Copyright 2021, Wiley–VCH GmBH. B Schematic illustration of DC activation and PD-1/PD-L1 blockade mediated by gCM@mnau for cancer immunotherapy, reprinted with permission [141]. Copyright 2024, American Chemical Society. C Schematic diagram of the antitumor mechanism of PtMnIr nanozymes, reprinted with permission [142]. Copyright 2023, Wiley–VCH GmbH. D Schematic illustration of synthesis and tumor catalytic immunotherapy of SS-MSN@Au-BOM, (a) SS-MSN were prepared by the one-pot method, and Au nanozyme was grown on the surface of SS-MSN through NaBH₄ reduction, reprinted with permission [143]. Copyright 2024, Wiley–VCH GmBH

Fig. 10

A Schematic of antitumor mechanism of CuCo₂S₄-Pt-PEG, (a) Illustration of the synthetic procedure of CuCo₂S₄-Pt-PEG, (b) Schematic of CuCo₂S₄-Pt-PEG with PTT/PDT/enzyme catalytic activity for synergetic therapy. Copyright 2024, Elsevier Ltd. [154]. B Schematic representation of the synthesis, trimodal imaging, and CDT-PTT of Ir@PLNPs@EM. Copyright 2024, Wiley–VCH GmBH [161]. C Schematic illustration for (a) the preparation of CPTH-AT nanozyme and (b) in vivo combined therapeutic of nanozymes-mediated biocatalytic immunotherapy and PTT. Copyright 2024, Elsevier Ltd. [162]. D (a) Synthesis of MLP@DHA&Ce6. (b) Schematic illustration of the mechanism behind MLP@DHA&Ce6-induced cell death, involving the generation of ROS from multiple sources [165]. Copyright (2023) American Chemical Society. E Schematic illustration of synergistic anti-tumor photodynamic therapy and immunotherapy based on CDK4/6 Nano PROTAC. Copyright 2024, Elsevier Ltd. [166]. F Synthesis and mechanism of action of Gd₂O₃/BSA@MoS₂-HA, (a) Synthetic route of Gd₂O₃/BSA@MoS₂-HA, (b) These nanoparticles could be applied for MSOT/CT/MR guided photothermal/radio combined cancer therapy, (c) After reaction with GSH, the NPs break down and are excreted out of the body. Reprinted with permission from [167]. Copyright (2024) American Chemical Society

Fig. 11

A Schematic illustrating the key steps in preparing the Au@Pt-Ce₆-HN-1 nanoplatform and its multimodal imaging-guided synergistic PDT/PTT/CDT antitumor mechanism. Copyright 2024, Elsevier Ltd. [179]. B Schematic illustration of (a) the synthetic procedure and (b) the antitumor mechanism of the Cu-MCGH nanocomposite. Copyright 2024, Wiley–VCH GmBH [187]. C Schematic illustration of the parachute-like APIJNS synergistic CDT/PTT/PDT. Copyright 2024, Wiley–VCH GmBH [188]. D Schematic illustration of Fe₃O₄@TiO₂/DOX microspheres and the combined CDT/PDT/PTT/chemotherapy for tumor inhibition. Copyright 2024, Nanomaterials [191]. E Schematic illustration of the sonoresponsive and NIR-II-photoresponsive CD/TiCN nanozymes for “three-in-one” multimodal oncotherapy. Copyright 2024, Wiley–VCH GmBH [194]. F Schematic diagram for the preparation of the Cu₂O@Au nanozyme and the proposed antitumor mechanism [195]