顺铂
纳米医学
谷胱甘肽
药理学
细胞凋亡
癌细胞
抗药性
化学
程序性细胞死亡
化疗
细胞毒性
毒性
癌症研究
癌症
体外
材料科学
生物化学
医学
生物
纳米技术
纳米颗粒
内科学
酶
有机化学
微生物学
作者
Yao Lu,Qingqing Pan,Wenxia Gao,Yuji Pu,Zhuangzhuang Zhang
摘要
Platinum-based chemotherapy is widely used to treat various cancers. However, exogenous platinum is likely to cause severe side effects and drug resistance induced by upregulated glutathione (GSH) in cancer cells poses a threat to the management of cancer progression and recurrence. Anticancer copper-organic complexes are excellent candidates to substitute platinum-based chemotherapeutics, exhibiting lower systemic toxicity and even overcoming platinum-based chemotherapy resistance. Here, we report the GSH-resistance of copper(II) bis(diethyldithiocarbamate) (CuET) and its reversal of cisplatin resistance in non-small-cell lung cancer via cuproptosis. Electrochemistry and UV-vis spectroscopy studies demonstrate that CuET possesses a lower reduction potential and the reaction inertness with GSH. Importantly, CuET overcomes the drug resistance of A549/DDP cells and the anticancer effect is hardly affected by intracellular GSH levels. To improve the solubility and bioavailability, bovine serum albumin-stabilized CuET nanoparticles (NPs) are prepared and they have a high drug loading content of 27.5% and excellent physiological stability. In vitro studies manifest that CuET NPs augment the distributions in the cytosol and cytoskeleton, inducing cell death via cuproptosis in A549/DDP cells, which is distinctly different from the apoptosis pattern induced by cisplatin. In vivo antitumor evaluation shows that the nanomedicine has superior biosafety and potent antitumor activity in a cisplatin-resistant tumor model. Our study suggests that copper-organic complex-based nanosystems could be a powerful toolbox to tackle the platinum-based drug resistance and systemic toxicity concerns.
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