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新型当归多糖仿生纳米载药系统用于姜黄素治疗肝细胞癌及免疫调节作用

Novel Chinese Angelica Polysaccharide Biomimetic Nanomedicine to Curcumin Delivery for Hepatocellular Carcinoma Treatment and Immunomodulatory Effect.

机构信息

School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai 264005, P.R. China.

School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai 264005, P.R. China; Weifang Institute of Chinese Medical Sciences and Industrial Technology, Weifang 261100, P.R.China.

出版信息

Phytomedicine. 2021 Jan;80:153356. doi: 10.1016/j.phymed.2020.153356. Epub 2020 Sep 25.

Abstract

BACKGROUND

Using natural polysaccharides from Traditional Chinese Medicine as nanodrug delivery systems have considerable potential for tumor diagnostics and therapeutics.

PURPOSE

On the basis of targeted therapy and combining the advantages of natural polysaccharides (angelica polysaccharide, APS) and natural Chinese medicine (curcumin, Cur) to design functionalized nanoparticles to improve the therapeutic through cell membrane encapsulation and immunotherapy.

STUDY DESIGN AND METHODS

Cur-loaded, glycyrrhetic acid (GA)-APS-disulfide bond (DTA)-Cur nanomicelle (GACS-Cur), which were prepared by the dialysis method. GACS-Cur was encapsulated with the membranes from red blood cells (RBCm) termed GACS-Cur@RBCm, which were prepared by the principle of extrusion using a miniature extruder. The developed formulations were subjected to various in vitro and in vivo evaluation tests.

RESULTS

The resulting APS nanocarriers supported a favorable drug-loading capacity, biocompatibility, and enhanced synergistic anti-hepatoma effects both in vitro and in vivo. After administration in mice, in vivo imaging results showed that the GACS-Cur and RBCm-coated groups had an obvious stronger tumor tissue targeting ability than the control treatment groups. Additionally, the immunomodulatory effect increased IL-12, TNF-α and IFN-γ expression and CD8+ T cell infiltration (1.9-fold) than that of the saline group. Notably, in comparison with hyaluronic acid (HA) nanocarriers, APS nanocarriers possess higher anti-hepatoma efficiency and targeting capabilities and, thus, should be further studied for a wide range of anti-cancer applications.

CONCLUSION

Our data demonstrated that APS nanocarriers encapsulated with erythrocyte membrane mighty be a promising clinical method in the development of efficacy, safety and targeting of liver cancer therapy.

摘要

背景

利用中药天然多糖作为纳米药物传递系统,在肿瘤诊断和治疗方面具有很大的潜力。

目的

在靶向治疗的基础上,结合天然多糖(当归多糖,APS)和天然中药(姜黄素,Cur)的优势,设计功能化纳米粒,通过细胞膜包封和免疫治疗提高治疗效果。

研究设计和方法

采用透析法制备载姜黄素、甘草酸(GA)-APS-二硫键(DTA)-姜黄素纳米胶束(GACS-Cur)。GACS-Cur 被称为 GACS-Cur@RBCm 的红细胞膜(RBCm)包封,这是通过使用微型挤出机挤出原理制备的。对开发的制剂进行了各种体外和体内评价测试。

结果

所得的 APS 纳米载体具有良好的载药能力、生物相容性和增强的协同抗肝癌作用,无论是在体外还是体内。在小鼠给药后,体内成像结果表明,GACS-Cur 和 RBCm 涂层组比对照组具有明显更强的肿瘤组织靶向能力。此外,免疫调节作用增加了 IL-12、TNF-α 和 IFN-γ 的表达和 CD8+T 细胞浸润(增加 1.9 倍)比生理盐水组。值得注意的是,与透明质酸(HA)纳米载体相比,APS 纳米载体具有更高的抗肝癌效率和靶向能力,因此,应该进一步研究用于广泛的抗癌应用。

结论

我们的数据表明,用红细胞膜包裹的 APS 纳米载体可能是一种有前途的临床方法,用于开发肝癌治疗的疗效、安全性和靶向性。

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