Recently, in a comprehensive review article published in Nature Reviews Bioengineering, a research team led by Prof. YAN Xiyun extensively reviewed the representative research progress of nanozyme catalysis in medicine, discussing feasible in vivo application design strategies and looking ahead at the challenges and prospects of clinical translation of nanozymes.

Oxidative stress is associated with various diseases and health issues, such as cancer, cardiovascular diseases, neurodegenerative diseases, and diabetes. Traditional oxidative stress regulation methods mainly rely on enzymes or small molecule drugs but are difficult to sufficiently meet clinical needs. This article introduces the potential of nanozymes as novel catalytic drugs for regulating oxidative stress.

Nanozymes exhibit high and persistent catalytic activity due to their stable structure and abundant catalytic sites. By adjusting nanostructures (such as size, shape, surface modifications) or changing catalytic environments (such as pH, temperature, ion strength), nanozymes can display diversified biocatalytic functions, making them easier to customize and design according to application requirements than enzymes.

Nanozymes, possessing multi-enzyme activity, can exert more potent effects than enzymes and small molecules via self-cascade catalysis. Additionally, the low immunogenicity and ease of enrichment at lesion sites make nanozymes more advantageous in catalytic medical applications compared to enzymes and small molecule drugs.

The article summarizes the positive outcomes of nanozymes in specific in vivo application scenarios, deeply analyzes the major limiting factors influencing treatment outcomes, and discusses key criteria for successful design. According to the overall catalytic roles of nanozymes, they can be classified into antioxidant nanozymes and pro-oxidant nanozymes. Antioxidant nanozymes are suitable for treating pathological conditions related to oxidative stress, while pro-oxidant nanozymes mainly work by promoting the generation of reactive oxygen species to kill tumors and combat bacteria.

Designing in vivo applications of nanozymes faces numerous challenges, including overcoming interference from biological components on their stability and catalytic activity, achieving targeted positioning in different tissues, selective elimination or generation of specific types of reactive oxygen species while maintaining biocompatibility and biodegradability. Formulating effective treatment strategies is more challenging due to the unclear role of reactive oxygen species in many diseases.

Therefore, a comprehensive understanding of the characteristics of nanozyme materials, biological systems, disease microenvironments, and their interactions is crucial for designing effective therapeutic nanozymes. The article also discusses the relationship between nanozyme catalytic performance, reactive oxygen species levels, and disease status in the outlook section, analyzing the challenges and prospects of in vivo application research and clinical translation, with a particular emphasis on the prerequisite of precise quantitative monitoring of in vivo catalytic reactions and ensuring the safety of nanomaterials for the successful clinical translation of nanozymes.

With the continuous discovery of nanozymes with unique biocatalytic activities, research on in vivo applications of nanozymes is evolving from primarily active oxygen regulation based on oxidoreductase activities to a broader spectrum. For example, currently, with careful design, nanozymes can be used in vivo for tracking or detecting tissue metabolic states to assist in disease diagnosis. These studies indicate broader application prospects for nanozymes in the field of biomedicine.

Article link: https://www.nature.com/articles/s44222-024-00205-1

Contact: FAN Kelong

Institute of Biophysics, Chinese Academy of Sciences

Beijing 100101, China

E-mail: fankelong@ibp.ac.cn

（Reported by Academician YAN Xiyun's group）