Nanoparticle-Mediated Delivery of Satraplatin to Overcome Cisplatin Drug Resistance

Drug resistance and cancer metastasis are the major obstacles for widely used platinum-based chemotherapy. It is acknowledgement that the decreasing intracellular accumulation of anticancer drugs and increasing sulfur-binding detoxification are two major mechanisms related to drug resistance. Herein...

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Published inJournal of functional biomaterials Vol. 14; no. 7; p. 387
Main Authors Jiang, Xiaohan, Yang, Qiang, Qi, Ruogu, Yan, Lesan
Format Journal Article
LanguageEnglish
Published Switzerland MDPI AG 01.07.2023
MDPI
Subjects
antitumor
Antitumor agents
Buthionine sulfoximine
Cancer
Cancer therapies
Care and treatment
Cell cycle
Chemotherapy
China
Cisplatin
Detoxification
drug delivery system
Drug resistance
Glutathione
Hemodialysis
Intracellular
Metastases
Morphology
Mortality
Nanoparticles
Ovarian cancer
platinum
Polyethylene glycol
Polymers
satraplatin
Signal transduction
Sulfur
Tumor cells
Tumors
Vitamin E
China
United States > US
Japan
platinum
satraplatin
drug delivery system
drug resistance
antitumor
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Summary:Drug resistance and cancer metastasis are the major obstacles for widely used platinum-based chemotherapy. It is acknowledgement that the decreasing intracellular accumulation of anticancer drugs and increasing sulfur-binding detoxification are two major mechanisms related to drug resistance. Herein, we developed a practical and straightforward method for formulating the clinically used anticancer drug satraplatin (JM-216) with D-α-tocopheryl polyethylene glycol succinate (TPGS)-based polymers to create satraplatin-loaded nanoparticles (SatPt-NPs). The experimental results demonstrate that SatPt-NPs exhibited comparable efficacy to A2780 in treating the A2780 cisplatin-resistant ovarian cancer cell line (A2780DDP), indicating their significant potential in overcoming drug resistance. Additionally, buthionine sulfoximine (BSO) is capable of depleting intracellular glutathione (GSH), resulting in reduced detoxification. After BSO treatment, the IC50 value of SatPt-NPs changed from 0.178 to 0.133 μM, which remained relatively unchanged compared to cisplatin. This suggests that SatPt-NPs can overcome drug resistance by evading GSH detoxification. Therefore, SatPt-NPs have the ability to inhibit drug resistance in tumor cells and hold tremendous potential in cancer treatment.
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These authors contributed equally to this work.
ISSN:2079-4983
2079-4983
DOI:10.3390/jfb14070387