Enhancing ovarian cancer treatment with maleimide-modified Pt(IV) prodrug nanoparticles

The limitations of platinum in ovarian cancer therapy, such as poor solubility and significant side effects, often lead to suboptimal therapeutic outcome and mortality. In this study, we have developed a novel approach utilizing biodegradable polymeric nanoparticles as a drug delivery system (NDDS),...

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Veröffentlicht in:Materials today bio 2024-08, Vol.27, p.101131, Article 101131
Hauptverfasser: Bai, Yiting, Wang, Zhenpeng, Liu, Dongzhen, Meng, Xiandi, Wang, Haorui, Yu, Meiling, Zhang, Songling, Sun, Tianmeng
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Sprache:eng
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Zusammenfassung:The limitations of platinum in ovarian cancer therapy, such as poor solubility and significant side effects, often lead to suboptimal therapeutic outcome and mortality. In this study, we have developed a novel approach utilizing biodegradable polymeric nanoparticles as a drug delivery system (NDDS), loaded with advanced platinum (IV) (Pt(IV)) prodrugs. A key feature of our approach is the enhancement of nanoparticles with maleimide, a modification hypothesized to significantly boost tumor tissue accumulation. When tested in mouse models of orthotopic and peritoneal metastasis ovarian cancer, these maleimide-modified nanoparticles are anticipated to show preferential accumulation in tumor tissues, enhancing therapeutic efficiency and minimizing systemic drug exposure. Our findings demonstrate that the maleimide-modified Pt(IV)-loaded NDDSs significantly reduce tumor burden in comparison to traditional cisplatin therapy, while simultaneously reducing adverse side effects. This leads to markedly improved survival rates in models of peritoneal metastasis ovarian cancer, offering a promising new direction in the treatment of this challenging disease. [Display omitted] •Developed Pt(IV) prodrug nano-formulations with optimal morphology and high drug loading for advanced ovarian cancer therapy.•Maleimide-modified PEG end-groups resulted in improved peritoneal retention and enhanced cellular uptake.•Pt(IV)@Mal-NPs improved tumor targeting and enabled a responsive action to the presence of GSH.•Pt(IV)@Mal-NPs surpassed the effectiveness of traditional cisplatin in tumor inhibition while maintaining safety.
ISSN:2590-0064
2590-0064
DOI:10.1016/j.mtbio.2024.101131