Nanoparticle-Mediated Delivery of Satraplatin to Overcome Cisplatin Drug Resistance.

Nanoparticle-Mediated Delivery of Satraplatin to Overcome Cisplatin Drug Resistance.
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DOI:
10.3390/jfb14070387
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发表时间:
2023-07-22
影响因子:
4.8
通讯作者:
--
中科院分区:
工程技术3区
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--
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耐药性和癌症转移是铂类化疗广泛应用的主要障碍。人们承认,抗癌药物细胞内积累的减少和硫结合解毒的增加是与耐药性相关的两个主要机制。在此,我们开发了一种实用且简单的方法,将临床使用的抗癌药物沙铂 (JM-216) 与基于 D-α-生育酚聚乙二醇琥珀酸酯 (TPGS) 的聚合物配制在一起,以创建负载沙铂的纳米颗粒 (SatPt-NPs)。实验结果表明,SatPt-NPs 在治疗 A2780 顺铂耐药卵巢癌细胞系 (A2780DDP) 方面表现出与 A2780 相当的功效,表明它们在克服耐药性方面具有巨大潜力。此外,丁硫氨酸亚砜亚胺 (BSO) 能够消耗细胞内谷胱甘肽 (GSH),从而导致解毒作用减弱。 BSO处理后,SatPt-NPs的IC50值从0.178变为0.133μM,与顺铂相比保持相对不变。这表明 SatPt-NPs 可以通过逃避 GSH 解毒来克服耐药性。因此,SatPt-NPs具有抑制肿瘤细胞耐药性的能力,在癌症治疗中具有巨大的潜力。
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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