Recent advances in anticancer metallodrugs based on gold complexes and clusters

In the field of metal-based anticancer agents, gold-based drugs, including gold coordination complexes and gold clusters, have emerged as one of the most promising research directions following platinum-based drugs, owing to their unique physicochemical properties and distinct anticancer mechanisms.

A research team led by Liang Zhao from Tsinghua University in Beijing, China recently summarized the applications of gold coordination complexes and gold clusters with well-defined structures in the field of cancer treatment.

The team published their review in Nano Research on March 25, 2026.

“In this review, we introduce Au(I) complexes, Au(III) complexes and gold clusters separately, summarizing the recent advances in the anticancer research of gold complexes and gold clusters with well-defined structures. Special emphasis is placed on the ligand design and structure-activity relationships of Au(I) complexes, the synthetic strategies and anticancer mechanisms of Au(III) complexes, as well as the characteristics of gold cluster drugs,” said Liang Zhao, corresponding author of the review paper, professor in the Department of Chemistry at Tsinghua University. Dr. Zhao is also affiliated with the Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), and has been dedicated to the research of metal clusters for a long time. 

During the search for non-platinum chemotherapeutic agents, gold-based drugs have attracted great interest among researchers. This is attributed to the similar coordination properties of Au(III) to those of Pt(Ⅱ). Furthermore, Au(I) possesses a higher reduction potential (1.69 V vs. SHE) than Pt(II) (1.18 V vs. SHE). This indicates that Au(I) is more prone to being reduced to Au(0) in the biological system, which can then be efficiently excreted through the body's metabolic processes.

Currently, it is recognized that, unlike platinum-based drugs, the primary mechanism of action of gold-based drugs is the inhibition of thioredoxin reductase (TrxR) activity, disruption of cellular redox homeostasis, excessive production of reactive oxygen species (ROS), and subsequent induction of cell apoptosis.

The research team summarizes the development of various gold-based drugs in this review, including Au(I) coordination complexes, Au(III) coordination complexes, and gold clusters with well-defined structures. Au(I)-based drugs are mostly linear coordination complexes, whose activity is regulated by ligands. Common ligands such as phosphine ligands and N-heterocyclic carbene (NHCs) can be designed and modified to optimize the lipophilicity, targeting ability and stability of Au(I) coordination complexes, thereby exerting potent cytotoxicity against various cancer cells.

In contrast, Au(III)-based drugs are four-coordinate complexes and are generally reduced to the more active Au(I) species in vivo to exert anticancer effects. Additionally, Au(III) complexes can directly act on the DNA of cancer cells or target mitochondria to achieve anticancer efficacy. 

Different from gold coordination complexes, gold clusters contain more gold atoms, which endows them with exceptional optical properties. Therefore, gold clusters can not only act as chemotherapeutic agents but also be applied in photothermal therapy (PTT) and photodynamic therapy (PDT), as well as serve as radiosensitizers for radiotherapy.

It remains challenging to improve the stability and selectivity of gold-based drugs in complex biological environments while protecting normal tissues from damage. Moreover, the specific targets and underlying chemical mechanisms of most Au complexes and clusters have not been fully elucidated. To address these issues, the research team anticipates that the future advancement of gold-based drugs will require continuous optimization of ligand structures to enhance stability and targeting selectivity, integration of multiple therapeutic approaches such as immunotherapy and PDT to improve efficacy, and utilization of techniques like electron microscopy for in-depth elucidation of their mechanisms of action in vivo.

This review provides a reference for the research on gold-based anticancer agents, and is expected to accelerate the development of structurally well-defined, highly effective, and low-toxicity gold-based drugs.

Other contributors include Xiaoni An from the Department of Chemistry at Tsinghua University in Beijing, China.

This work was supported by the National Natural Science Foundation of China (22025105and 22350002).

DOI Link:

https://doi.org/10.26599/NR.2026.94908509

About Nano Research

Nano Research is a peer-reviewed, open access, international and interdisciplinary research journal, sponsored by Tsinghua University and the Chinese Chemical Society, published by Tsinghua University Press on the platform SciOpen. It publishes original high-quality research and significant review articles on all aspects of nanoscience and nanotechnology, ranging from basic aspects of the science of nanoscale materials to practical applications of such materials. After 18 years of development, it has become one of the most influential academic journals in the nano field. Nano Research has published more than 1,000 papers every year from 2022, with its cumulative count surpassing 8,000 articles. In 2025 InCites Journal Citation Reports, its 2025 IF is 9.4 (8.3, 5 years), and it continues to be the Q1 area among the four subject classifications. Nano Research Award, established by Nano Research together with TUP and Springer Nature in 2013, and Nano Research Young Innovators (NR45) Awards, established by Nano Research in 2018, have become international academic awards with global influence.