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Self-assembled metal-phenolic network nanoparticles for delivery of a cisplatin prodrug for synergistic chemo-immunotherapy.
- Source :
-
Biomaterials science [Biomater Sci] 2024 Jul 09; Vol. 12 (14), pp. 3649-3658. Date of Electronic Publication: 2024 Jul 09. - Publication Year :
- 2024
-
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 (Fe <superscript>3+</superscript> ) through coordination reactions between Fe <superscript>3+</superscript> 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 <subscript>2</subscript> O <subscript>2</subscript> level through cascade reactions. This is further utilized to produce highly toxic hydroxyl radicals (˙OH) catalyzed by the Fe <superscript>3+</superscript> -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.
- Subjects :
- Humans
Animals
Mice
Immunotherapy methods
Nanoparticles chemistry
Nanoparticles administration & dosage
Dendritic Cells drug effects
Glutathione chemistry
Glutathione metabolism
Cell Line, Tumor
Iron chemistry
Drug Carriers chemistry
Phenols chemistry
Phenols pharmacology
Phenols administration & dosage
Cisplatin pharmacology
Cisplatin chemistry
Cisplatin administration & dosage
Prodrugs chemistry
Prodrugs pharmacology
Prodrugs administration & dosage
Antineoplastic Agents chemistry
Antineoplastic Agents pharmacology
Antineoplastic Agents administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 2047-4849
- Volume :
- 12
- Issue :
- 14
- Database :
- MEDLINE
- Journal :
- Biomaterials science
- Publication Type :
- Academic Journal
- Accession number :
- 38857014
- Full Text :
- https://doi.org/10.1039/d4bm00650j