Novel co-delivery of oridonin and docetaxel nanoliposome for an enhanced antitumor effect on esophageal cancer

IF 3.2 4区医学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Journal of Gene Medicine Pub Date : 2024-08-12 DOI:10.1002/jgm.3725

Xi Chen, Hengyu Mao, Feng Peng, Jiang Fan, Fu Yang

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引用次数: 0

Abstract

Introduction

Esophageal cancer is one of the major cancers in China. Most patients with esophageal cancer are diagnosed at an advanced stage, and the 5 year survival rate is discouraging. Combined chemotherapy is a common method for the treatment of esophageal cancer.

Methods

In this study, distearoyl phosphatidyl ethanolamine polyethylene glycol 2000 (DSPE-PEG2000) nanoliposomes (NLPs) encapsulating the anticancer drugs docetaxel (DOX) and oridonin (ORD) were prepared, and their ability to enhance the release of anticancer drugs was determined. The NLP system was characterized by transmission electron microscopy, particle size and encapsulation efficiency. In addition, the release characteristics and pharmacodynamics of these drugs were also studied in detail.

Results

When the DOX/ORD ratio was 2:1, the higher proportion of DOX led to a stronger synergy effect. DOX/ORD NLPs were prepared by the high-pressure homogenization method and had a uniform spherical morphology. The mean particle size and polydispersity index were determined to be 246.4 and 0.163, respectively. The stability results showed that no significant change was observed in particle size, zeta potential, Encapsulation efficiency and dynamic light scattering for DOX/ORD NLPs during the observation period. The results of in vitro release illustrated that the acidic environment of tumor might be beneficial to drug release. The three-dimensional tumorsphere showed that DOX/ORD NLPs can reach the interior of tumor spheres, which destroys the structure of cells, resulting in irregular spherical tumor spheres. The in vivo study results indicated that DOX/ORD NLPs had an obvious targeting effect on subcutaneous tumors and have the potential to actively deliver drugs to tumor tissues. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was used to detect apoptosis. The results showed that DOX/ORD NLP treatment could significantly induce apoptosis and inhibit tumor growth.

Conclusion

The DOX/ORD NLPs prepared in this study can enhance the anti-tumor activity, and are expected to be a promising co-delivery platform for the treatment of esophageal cancer.

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新型奥利多宁和多西他赛纳米脂质体联合给药增强食管癌的抗肿瘤效果

简介食管癌是中国的主要癌症之一。大多数食管癌患者确诊时已是晚期，5 年生存率令人沮丧。联合化疗是治疗食管癌的常用方法：本研究制备了包裹抗癌药物多西他赛（DOX）和奥利多宁（ORD）的二硬脂酰磷脂酰乙醇胺聚乙二醇 2000（DSPE-PEG2000）纳米脂质体（NLPs），并测定了其增强抗癌药物释放的能力。通过透射电子显微镜、粒度和封装效率对 NLP 系统进行了表征。此外，还详细研究了这些药物的释放特性和药效学：结果：当 DOX/ORD 的比例为 2:1 时，DOX 的比例越高，协同效应越强。采用高压均质法制备的 DOX/ORD NLPs 具有均匀的球形形态。平均粒径和多分散指数分别为 246.4 和 0.163。稳定性结果表明，在观察期内，DOX/ORD NLPs 的粒度、ZETA电位、包封效率和动态光散射均无明显变化。体外释放结果表明，肿瘤的酸性环境可能有利于药物的释放。三维肿瘤球显示，DOX/ORD NLPs能到达肿瘤球内部，破坏细胞结构，形成不规则球形肿瘤球。体内研究结果表明，DOX/ORD NLPs 对皮下肿瘤有明显的靶向作用，具有向肿瘤组织主动递送药物的潜力。末端脱氧核苷酸转移酶dUTP缺口标记（TUNEL）染色用于检测细胞凋亡。结果表明，DOX/ORD NLP处理可显著诱导细胞凋亡并抑制肿瘤生长：结论：本研究制备的 DOX/ORD NLPs 可增强抗肿瘤活性，有望成为治疗食管癌的联合给药平台。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Gene Medicine 医学-生物工程与应用微生物

CiteScore

6.40

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： The aims and scope of The Journal of Gene Medicine include cutting-edge science of gene transfer and its applications in gene and cell therapy, genome editing with precision nucleases, epigenetic modifications of host genome by small molecules, siRNA, microRNA and other noncoding RNAs as therapeutic gene-modulating agents or targets, biomarkers for precision medicine, and gene-based prognostic/diagnostic studies. Key areas of interest are the design of novel synthetic and viral vectors, novel therapeutic nucleic acids such as mRNA, modified microRNAs and siRNAs, antagomirs, aptamers, antisense and exon-skipping agents, refined genome editing tools using nucleic acid /protein combinations, physically or biologically targeted delivery and gene modulation, ex vivo or in vivo pharmacological studies including animal models, and human clinical trials. Papers presenting research into the mechanisms underlying transfer and action of gene medicines, the application of the new technologies for stem cell modification or nucleic acid based vaccines, the identification of new genetic or epigenetic variations as biomarkers to direct precision medicine, and the preclinical/clinical development of gene/expression signatures indicative of diagnosis or predictive of prognosis are also encouraged.