Citation: Muhammad Nafees, Muhammad Hanif, Piaoping Yang. Metallodrugs: From mere cytotoxic agents to immune modulators and checkpoint inhibitors[J]. Chinese Chemical Letters, ;2026, 37(4): 111013. doi: 10.1016/j.cclet.2025.111013 shu

Metallodrugs: From mere cytotoxic agents to immune modulators and checkpoint inhibitors

Muhammad Nafees ^{a, *,} ,
Muhammad Hanif ^{b, *,} ,
Piaoping Yang ^{a, *,}

a.
Key Laboratory of Superlight Materials and Surface Technology, Ministry of Education, College of Materials Science and Chemical Engineering, Harbin Engineering University, Harbin 150000, China
b.
School of Chemical Sciences, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand

nafees@hrbeu.edu.cn

m.hanif@auckland.ac.nz

yangpiaoping@hrbeu.edu.cn

Received Date: 19 November 2024
Revised Date: 26 February 2025
Accepted Date: 27 February 2025
Available Online: 28 February 2025

Figures(9)

Traditional chemotherapeutic approaches lack selectivity and damage both cancerous and healthy cells. In contrast, cancer immunotherapy harnesses the host's immune system to selectively target and eradicate tumor cells, offering tremendous potential for the long-term suppression of tumor growth and preventing its recurrence. However, tumors often develop immune evasion by exploiting immune checkpoints, which regulate the immune system. Among these checkpoints, programmed death protein 1 (PD-1) and its ligand (PD-L1) have garnered significant interest because they play a key role in protecting the tumor cells from immune-mediated eradication. The approval of monoclonal antibodies (mAbs) that target PD-1/PD-L1 by the Food and Drug Administration (FDA) is a milestone in immunotherapy. Although mAbs have demonstrated remarkable success in treating skin melanomas, their efficacy against other solid tumors remains limited. There is a clear need to explore new approaches to enhance the efficacy of mAbs and find more effective checkpoint inhibitors. Metal-based drugs offer a new platform to address this challenge. This review highlights the recent progress in leveraging metal complexes as PD-1/PD-L1 inhibitors. We discussed metal-based agents used either alone or in combination with mAbs to boost the immune system. We also highlighted examples of metallodrugs encapsulated within the nanoparticles to augment the efficacy of immune checkpoint therapy. While research on metal-based complexes targeting PD-1/PD-L1 is still in its infancy, the examples presented here will serve as the basis for future discussions and efforts in this emerging field. We anticipate that ongoing research in targeting immune checkpoint blockade with innovative metal-based therapeutics will enhance the scope of treatment across a wide range of cancers.
- Immunogenic cell death,
- Immune checkpoint blockade,
- Metal complex,
- Anticancer agents,
- Monoclonal antibodies,
- PD-1/PD-L1 inhibition,
- Cold vs. hot tumors,
- Chemo-immunotherapy
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沈阳化工大学材料科学与工程学院沈阳 110142