The treatment of hepatocellular carcinoma with SP94 modified asymmetrical bilayer lipid-encapsulated Cu(DDC)₂ nanoparticles facilitating Cu accumulation in the tumor.

IF 5 2区医学 Q1 PHARMACOLOGY & PHARMACY Expert Opinion on Drug Delivery Pub Date : 2023-01-01 DOI:10.1080/17425247.2023.2155631

Hao Liu, Yihan Kong, Xue Liang, Zixu Liu, Xueting Guo, Bing Yang, Tian Yin, Haibing He, Jingxin Gou, Yu Zhang, Xing Tang

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引用次数: 1

Abstract

Background: Copper diethyldithiocarbamate (Cu(DDC)₂) has been demonstrated to possess excellent antitumor activity. However, the extremely poor water solubility of Cu(DDC)₂ bring difficulty for its formulation research. In this study, we aim to develop a novel nanocarrier for Cu(DDC)₂ delivery to overcome this obstacle and enhance antitumor activity.

Methods: The SP94 modified asymmetrical bilayer lipid-encapsulated Cu(DDC)₂ nanoparticles (DCDP) was established by combining the method of inverse microemulsion aggregation and thin-film dispersion. In vitro cellular assays and in vivo tumor-xenograft experiments were conducted to evaluate the tumor chemotherapeutic effect of DCDP. And the vital role of copper ions played in DSF or DDC (DSF/DDC)-based cancer chemotherapy was also explored.

Results: DCDP with an encapsulation efficiency (EE%) of 74.0% were successfully prepared. SP94 modification facilitated cellular intake for DCDP, and promoted apoptosis to repress tumor cell proliferation (IC₅₀, 200 nM). And DCDP effectively inhibited tumor growth with a high tumor inhibition rate of 74.84%. Furthermore, Cu(DDC)₂ was found to facilitate the copper ion accumulation in tumor tissues, which is beneficial to therapy with high potency.

Conclusion: DCDP exhibited high-efficient tumor chemotherapeutic efficacy and provided a novel strategy for investigating the anticancer mechanism of Cu(DDC)₂.

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SP94修饰的不对称双层脂包Cu(DDC)2纳米颗粒促进Cu在肿瘤中的蓄积治疗肝细胞癌

背景:二乙基二硫代氨基甲酸铜(Cu(DDC)2)已被证明具有良好的抗肿瘤活性。然而，Cu(DDC)2极差的水溶性给其配方研究带来了困难。在这项研究中，我们的目标是开发一种新的纳米载体来递送Cu(DDC)2，以克服这一障碍，提高抗肿瘤活性。方法:采用微乳液反聚和薄膜分散相结合的方法，制备SP94修饰的不对称双层脂包Cu(DDC)2纳米粒子(DCDP)。通过体外细胞实验和体内肿瘤异种移植实验来评价DCDP的肿瘤化疗效果。并探讨了铜离子在DSF或DDC (DSF/DDC)为基础的肿瘤化疗中的重要作用。结果:成功制备了包封率为74.0%的DCDP。SP94修饰促进细胞摄取DCDP，促进细胞凋亡抑制肿瘤细胞增殖(IC50, 200 nM)。DCDP有效抑制肿瘤生长，肿瘤抑制率高达74.84%。此外，发现Cu(DDC)2促进了肿瘤组织中铜离子的积累，有利于高效治疗。结论:DCDP具有高效的肿瘤化疗效果，为研究Cu(DDC)2的抗癌机制提供了新的策略。

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来源期刊

Expert Opinion on Drug Delivery 医学-药学

CiteScore

11.10

自引率

3.00%

发文量

104

审稿时长

3 months

期刊介绍： Expert Opinion on Drug Delivery (ISSN 1742-5247 [print], 1744-7593 [electronic]) is a MEDLINE-indexed, peer-reviewed, international journal publishing review articles covering all aspects of drug delivery research, from initial concept to potential therapeutic application and final relevance in clinical use. Each article is structured to incorporate the author’s own expert opinion on the scope for future development.