Diethyldithiocarbamate copper nanoparticle overcomes resistance in cancer therapy without inhibiting P-glycoprotein

IF 4.7 4区医学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Nanomedicine: Nanotechnology, Biology and Medicine Pub Date : 2023-01-01 DOI:10.1016/j.nano.2022.102620

Xuejia Kang Ms , Junwei Wang Ms , Chung-Hui Huang Bs , Fajar Setyo Wibowo Ms , Rajesh Amin PhD , Pengyu Chen PhD , Feng Li PhD

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引用次数: 9

Abstract

Copper diethyldithiocarbamate [Cu(DDC)₂] is a promising anticancer agent. However, its poor water solubility is a significant obstacle to clinical application. In previous studies, we developed a stabilized metal ion ligand complex (SMILE) method to prepare Cu(DDC)₂ nanoparticle (NP) to address the drug delivery challenge. In the current study, we investigate the use of Cu(DDC)₂ NP for treating P-glycoprotein (P-gp) mediated drug-resistant cancers. We tested its anticancer efficacy with extensive in vitro cell-based assays and in vivo xenograft tumor model. We also explored the mechanism of overcoming drug resistance by Cu(DDC)₂ NP. Our results indicate that Cu(DDC)₂ NP is not a substrate of P-gp and thus can avoid P-gp mediated drug efflux. Further, the Cu(DDC)₂ NP does not inhibit the activity or the expression of P-gp.

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二乙基二硫代氨基甲酸铜纳米颗粒在不抑制p糖蛋白的情况下克服了癌症治疗的耐药性

二乙基二硫代氨基甲酸铜[Cu(DDC)2]是一种很有前途的抗癌药物。但其水溶性差是临床应用的一大障碍。在之前的研究中，我们开发了一种稳定的金属离子配体络合物(SMILE)方法来制备Cu(DDC)2纳米颗粒(NP)，以解决药物递送的挑战。在目前的研究中，我们研究了Cu(DDC)2 NP在治疗p糖蛋白(P-gp)介导的耐药癌症中的应用。我们通过广泛的体外细胞实验和体内异种移植肿瘤模型来测试其抗癌功效。我们还探讨了Cu(DDC) 2np克服耐药的机制。我们的研究结果表明Cu(DDC)2 NP不是P-gp的底物，因此可以避免P-gp介导的药物外排。此外，Cu(DDC)2 NP不抑制P-gp的活性或表达。

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来源期刊

Nanomedicine: Nanotechnology, Biology and Medicine 医学-纳米科技

CiteScore

8.10

自引率

3.60%

发文量

104

审稿时长

4.6 months

期刊介绍： Nanomedicine: Nanotechnology, Biology and Medicine (NBM) is an international, peer-reviewed journal presenting novel, significant, and interdisciplinary theoretical and experimental results related to nanoscience and nanotechnology in the life and health sciences. Content includes basic, translational, and clinical research addressing diagnosis, treatment, monitoring, prediction, and prevention of diseases.