Self-assembled metal-phenolic network nanoparticles for delivery of a cisplatin prodrug for synergistic chemo-immunotherapy.
Xingzu ZhangQingyu ZongTaian LinIhsan UllahMaolin JiangSiyi ChenWenjie TangYuan GuoYouyong YuanJin-Zhi DuPublished in: Biomaterials science (2024)
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 (Fe 3+ ) through coordination reactions between Fe 3+ 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 H 2 O 2 level through cascade reactions. This is further utilized to produce highly toxic hydroxyl radicals (˙OH) catalyzed by the Fe 3+ -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.
Keyphrases
- cancer therapy
- cell death
- dendritic cells
- oxidative stress
- induced apoptosis
- cell cycle arrest
- fluorescent probe
- photodynamic therapy
- squamous cell carcinoma
- metabolic syndrome
- reactive oxygen species
- radiation therapy
- cell proliferation
- early onset
- room temperature
- sensitive detection
- combination therapy
- locally advanced
- heat shock protein