A Targeted Redox‐Active Dual‐Action Pt(IV)‐Mn(II) Prodrug Displays Enhanced In Vivo Anticancer Activity

A Targeted Redox‐Active Dual‐Action Pt(IV)‐Mn(II) Prodrug Displays Enhanced In Vivo Anticancer Activity

Advanced Healthcare Materials

10.1002/adhm.202501847

https://doi.org/10.1002/adhm.202501847

Alvaro Lopez‐Sanchez, Henri Chédotal, Ram Pravin Kumar Muthuramalingam, Marine Thomas, Jia Ning Nicolette Yau, Priya Ranjan Sahoo, Clotilde Policar, Frédéric Batteux, Kadda Medjoubi, Andrea Somogyi, Giulia Adriani, Carole Nicco, Romain Coriat, Giorgia Pastorin, Hélène C. Bertrand

3D cell culture, Chemoresistance, Platinum prodrug, microfluidics, Colorectal cancer, Reactive Oxygen Species (ROS), PEGylated micelles

06 July 2025

Lopez‐Sanchez, A., Chédotal, H., Muthuramalingam, R. P. K., Thomas, M., Yau, J. N. N., Sahoo, P. R., Policar, C., Batteux, F., Medjoubi, K., Somogyi, A., Adriani, G., Nicco, C., Coriat, R., Pastorin, G., & Bertrand, H. C. (2025). A Targeted Redox‐Active Dual‐Action Pt(IV)‐Mn(II) Prodrug Displays Enhanced In Vivo Anticancer Activity. Advanced Healthcare Materials. Portico. https://doi.org/10.1002/adhm.202501847

FDA‐approved platinum (Pt) anticancer drugs (e.g. cisplatin, oxaliplatin and carboplatin) grapple with clinical challenges including chemoresistance and systemic side‐effects, Pt(IV) prodrugs have emerged as potent alternative chemotherapies. In this work, a novel bimetallic dual‐action Pt(IV) prodrug bearing a manganese (Mn) superoxide dismutase mimic (SODm) is presented, demonstrating high stability in solution. The prodrug displays intrinsic antisuperoxide properties and in vitro comparable cytotoxic activities to that of oxaliplatin in 2‐ and 3D colorectal cancer cellular models, as well as an increase in intracellular reactive oxygen species (ROS) production. The prodrug is further evaluated in an in vivo mice model for colorectal cancer, demonstrating a similar performance to that of oxaliplatin. Additionally, a total tumor remission is reached with a PEGylated micellar encapsulation of the prodrug. This novel formulation increases the lifetime of the prodrug and therefore its tumoral uptake and plasma content with respect to the unencapsulated drug. This enhanced activity suggests the therapeutic potential of said formulation.

Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)

This research is supported by core funding from: Singapore Immunology Network (A*STAR)
Grant Reference no. :

© 2025 The Author(s). Advanced Healthcare Materials published by Wiley-VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

https://oar.a-star.edu.sg/communities-collections/articles/22008

2192-2640
2192-2659

Singapore Immunology Network

https://doi.org/10.1002/adhm.202501847