Issue 14, 2024

Self-assembled metal–phenolic network nanoparticles for delivery of a cisplatin prodrug for synergistic chemo-immunotherapy

Abstract

Despite cisplatin's pivotal role in clinically proven anticancer drugs, its application has been hampered by severe side effects and a grim prognosis. Herein, we devised a glutathione (GSH)-responsive nanoparticle (PFS-NP) that integrates a disulfide bond-based amphiphilic polyphenol (PP-SS-DA), a dopamine-modified cisplatin prodrug (Pt-OH) and iron ions (Fe3+) through coordination reactions between Fe3+ and phenols. After entering cells, the responsively released Pt-OH and disulfide bonds eliminate the intracellular GSH, in turn disrupting the redox homeostasis. Meanwhile, the activated cisplatin elevates the intracellular H2O2 level through cascade reactions. This is further utilized to produce highly toxic hydroxyl radicals (˙OH) catalyzed by the Fe3+-based Fenton reaction. Thus, the amplified oxidative stress leads to immunogenic cell death (ICD), promoting the maturation of dendritic cells (DCs) and ultimately activating the anti-tumor immune system. This innovative cisplatin prodrug nanoparticle approach offers a promising reference for minimizing side effects and optimizing the therapeutic effects of cisplatin-based drugs.

Graphical abstract: Self-assembled metal–phenolic network nanoparticles for delivery of a cisplatin prodrug for synergistic chemo-immunotherapy

Supplementary files

Article information

Article type
Paper
Submitted
10 May 2024
Accepted
30 May 2024
First published
31 May 2024

Biomater. Sci., 2024,12, 3649-3658

Self-assembled metal–phenolic network nanoparticles for delivery of a cisplatin prodrug for synergistic chemo-immunotherapy

X. Zhang, Q. Zong, T. Lin, I. Ullah, M. Jiang, S. Chen, W. Tang, Y. Guo, Y. Yuan and J. Du, Biomater. Sci., 2024, 12, 3649 DOI: 10.1039/D4BM00650J

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