Single‐atom nanozyme (SAzyme) with peroxidase‐like activity can alter cellular redox balance and shows promising potential for tumor therapy. However, the “cold” immune microenvironment and limited amount of hydrogen peroxide (H2O2) in solid tumors severely restrict its efficacy. Herein, a light‐controlled oxidative stress amplifier system is designed by co‐encapsulating Pd‐C SAzymes and camptothecin in agarose hydrogel, which exhibits enhanced synergistic antitumor activity by self‐producing H2O2 and transforming “cold” tumors. In this nanozyme hydrogel system, the Pd‐C SAzyme converts near‐infrared laser into heat, resulting in agarose degradation and consequent camptothecin release. The camptothecin increases H2O2 level in tumors by activating nicotinamide adenine dinucleotide phosphate oxidase, improving the catalytic performance of SAzymes with peroxidase‐like activity. Moreover, the combination of photothermal therapy, chemotherapy, and nanozyme‐based catalytic therapy further facilitates tumor immunogenic death and enhanced antitumor immunity. The results reveal the synergistic antitumor potential of the novel SAzyme/chemotherapeutics‐based hydrogel system.

H2O2 Self‐Producing Single‐Atom Nanozyme Hydrogels as Light‐Controlled Oxidative Stress Amplifier for Enhanced Synergistic Therapy by Transforming “Cold” Tumors

Advances of nanoparticles as drug delivery systems for disease diagnosis and treatment

Nanozyme is a series of nanomaterials with enzyme-mimetic activities that can proceed with the catalytic reactions of natural enzymes. In the field of biomedicine, nanozymes are capturing tremendous attention due to their high stability and low cost. Enzyme-mimetic activities of nanozymes can be regulated by multiple factors, such as the chemical state of metal ion, pH, hydrogen peroxide (H2O2), and glutathione (GSH) level, presenting great promise for biomedical applications. Over the past decade, multi-functional nanozymes have been developed for various biomedical applications. To promote the understandings of nanozymes and the development of novel and multifunctional nanozymes, we herein provide a comprehensive review of the nanozymes and their applications in the biomedical field. Nanozymes with versatile enzyme-like properties are briefly overviewed, and their mechanism and application are discussed to provide understandings for future research. Finally, underlying challenges and prospects of nanozymes in the biomedical frontier are discussed in this review. 

https://jnanobiotechnology.biomedcentral.com/track/pdf/10.1186/s12951-022-01295-y

Nanozymes-recent development and biomedical applications

Chemodynamic therapy (CDT) has emerged to be a frontrunner amongst reactive oxygen species-based cancer treatment modalities. CDT utilizes endogenous H2O2 in tumor microenvironment (TME) to produce cytotoxic hydroxyl radicals (•OH) via Fenton or Fenton-like reactions. While possessing advantages such as tumor specificity, no need of external stimuli, and low side effects, practical applications of CDT are still impeded owing to the heterogeneity, complexity, and reductive environment of TME. Over the past couple of years, strategies to enhance CDT for efficient tumor regression are in rapid development in synergy with the growth of nanomedicine. In this review, we initially outline the fundamental understanding of Fenton and Fenton-like reactions and their relationship with CDT. Subsequently, the development in the design of nanosystems for CDT is highlighted in a general manner. Furthermore, recent advancement of the strategies to augment Fenton reactions in TME for enhanced CDT is discussed in detail. Finally, perspectives toward the future development of CDT for better therapeutic outcome are presented. This review is expected to draw attention for collaborative research on CDT in the best interest of its future clinical applications. 

Strategies for enhancing cancer chemodynamic therapy performance

Sp1-mediated upregulation of Prdx6 expression prevents podocyte injury in diabetic nephropathy via mitigation of oxidative stress and ferroptosis

As next-generation artificial enzymes, nanozymes have shown great promise for tumor catalytic therapy. In particular, their peroxidase-like activity has been employed to catalyze hydrogen peroxide (H2O2) to produce highly toxic hydroxyl radicals (•OH) to kill tumor cells. However, limited by the low affinity between nanozymes with H2O2 and the low level of H2O2 in the tumor microenvironment, peroxidase nanozymes usually produced insufficient •OH to kill tumor cells for therapeutic purposes. Herein, we present a pyrite peroxidase nanozyme with ultrahigh H2O2 affinity, resulting in a 4144- and 3086-fold increase of catalytic activity compared with that of classical Fe3O4 nanozyme and natural horseradish peroxidase, respectively. We found that the pyrite nanozyme also possesses intrinsic glutathione oxidase-like activity, which catalyzes the oxidation of reduced glutathione accompanied by H2O2 generation. Thus, the dual-activity pyrite nanozyme constitutes a self-cascade platform to generate abundant •OH and deplete reduced glutathione, which induces apoptosis as well as ferroptosis of tumor cells. Consequently, it killed apoptosis-resistant tumor cells harboring KRAS mutation by inducing ferroptosis. The pyrite nanozyme also exhibited favorable tumor-specific cytotoxicity and biodegradability to ensure its biosafety. These results indicate that the high-performance pyrite nanozyme is an effective therapeutic reagent and may aid the development of nanozyme-based tumor catalytic therapy.

Chaoyi Hong

Papers

High-Performance Self-Cascade Pyrite Nanozymes for Apoptosis–Ferroptosis Synergistic Tumor Therapy

Nanozyme: A promising tool from clinical diagnosis and environmental monitoring to wastewater treatment