Mesoporous zinc-polyphenol nanozyme for attenuating renal ischemia–reperfusion injury

Abstract

Aim: To target the reactive oxygen species (ROS) accumulation and renal tubular epithelial cell (rTEC) death in renal ischemia–reperfusion injury (IRI), we constructed a nanoparticle that offers ROS scavenging and rTEC-death inhibition: mesoporous zinc–tannic acid nanozyme (ZnTA). Materials & methods: After successfully constructing ZnTA, we proceeded to examine its effect on ROS accumulation, cellular ferroptosis and apoptosis, as well as injury severity. Results: Malondialdehyde, Fe²⁺ amounts and 4-HNE staining demonstrated that ZnTA effectively attenuated rTEC ferroptosis. TUNEL staining confirmed that Zn²⁺ carried by ZnTA could effectively inhibit caspase 3 and caspase 9, mitigating apoptosis. Finally, it reduced renal IRI through the synergistic effect of ROS scavenging and cell-death inhibition. Conclusion: This study is expected to provide a paradigm for a combined therapeutic strategy for renal IRI.

Article highlights

• In this study, zinc–tannic acid nanozyme (ZnTA) was synthesized using natural plant polyphenol tannic acid.

• This study explored the morphological characteristics of ZnTA in detail.

• ZnTA has excellent reactive oxygen species scavenging effect.

• ZnTA was observed to effectively inhibit ferroptosis in both in vitro and in vivo experiments.

• The morphological characteristics of mitochondria after ZnTA treatment were examined using electron microscopy.

• Zn²⁺ in ZnTA inhibited the expression of caspase 3 and 9.

• Apoptosis inhibition was observed after ZnTA treatment.

• ZnTA can effectively alleviate renal IRI.

Keywords: :

• ferroptosis
• mesoporous nanoparticles
• metal–polyphenol hybrids
• renal ischemia–reperfusion injury
• ROS scavenging

Supplemental material

Supplemental data for this article can be accessed at https://doi.org/10.1080/17435889.2024.2382667

Acknowledgments

The authors declare that they have no competing interests.

Author contributions

Z Li: Investigation, methodology, data curation, formal analysis, software, validation, writing-original draft. J Qin: Conceptualization, methodology, formal analysis, writing-review & editing. Y Feng.: Investigation, data curation, formal analysis, software, validation. C Ding: Conceptualization, re-sources, project administration, writing-review & editing, resources, supervision, funding acquisition. Y Guo.: Data curation. Z Zhao.: Investigation, formal analysis. S Sun: Investigation, writing-review & editing. J Zheng: Data curation. M Zhang: Writing-review & editing, formal analysis. J Zhang: Investigation, formal analysis. Y Zhang: Writing-review & editing. J Wei: Writing-review & editing, resources, supervision, funding acquisition. W Xue: Conceptualization, writing-review & editing, resources, supervision, funding acquisition, project administration.

Financial disclosure

This work was supported by the National Natural Science Foundation of China (82070768), the First Affiliated Hospital of Xi'an Jiaotong University (YGJC202209). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

All animal experiments were approved by the University Animal Care and Use Committee of Xi'an Jiaotong University (XJTUAE2023-267).

Data availability statement

All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (82070768), the First Affiliated Hospital of Xi'an Jiaotong University (YGJC202209).