Preparation of Glutathione-Regulated Sorafenib Targeted Nanodrug Delivery System and Its Antihepatocellular Carcinoma Activity

IF 8.3 2区材料科学 Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY

ACS Applied Materials & Interfaces Pub Date : 2024-11-13 DOI:10.1021/acsami.4c11076

Yijun Wu, Xiaochen Wang, Longxia Li, Mingyang Wang, Sui Tian, Jinfeng Song, Yunfeng Ma

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Abstract

To enhance the therapeutic effect of sorafenib (SOR) on liver cancer, we have developed a targeted nanodrug delivery system with glutathione (GSH) downregulation functionality. The preparation process comprises the synthesis of amino-functionalized mesoporous silica nanoparticles (MSN-NH₂), surface modification with ethacrynic acid (EA), loading of SOR into the pores, and final surface coating with hyaluronic acid (HA) to obtain SOR@MSN-EA@HA (SMEH) nanoparticles. SMEH nanoparticles specifically enter tumor cells via CD₄₄ receptor-mediated endocytosis. EA binds to GSH to consume it, while SOR is slowly released from the pores to exert antitumor effects while inhibiting GSH production. This results in sustained oxidative stress in the cells, thus enhancing the antitumor efficacy. Both in vitro and in vivo antitumor experiments as well as hemolysis tests have demonstrated that SMEH nanoparticles can accurately target liver cancer cells, effectively downregulate GSH concentration, exhibit good antitumor effects, and possess excellent safety, showing great potential in tumor treatment.

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谷胱甘肽调控的索拉非尼靶向纳米给药系统的制备及其抗肝癌活性

为了增强索拉非尼（SOR）对肝癌的治疗效果，我们开发了一种具有谷胱甘肽（GSH）下调功能的靶向纳米给药系统。制备过程包括合成氨基功能化介孔二氧化硅纳米颗粒（MSN-NH2）、用乙丙酸（EA）进行表面修饰、将索拉非尼（SOR）载入孔隙，最后用透明质酸（HA）进行表面包覆，得到SOR@MSN-EA@HA（SMEH）纳米颗粒。SMEH 纳米粒子通过 CD44 受体介导的内吞作用特异性地进入肿瘤细胞。EA 与 GSH 结合以消耗 GSH，而 SOR 则从孔中缓慢释放，在抑制 GSH 生成的同时发挥抗肿瘤作用。这将导致细胞内持续的氧化应激，从而增强抗肿瘤功效。体外、体内抗肿瘤实验和溶血试验均证明，SMEH 纳米粒子能准确靶向肝癌细胞，有效降低 GSH 浓度，具有良好的抗肿瘤效果，且安全性极高，在肿瘤治疗方面具有巨大潜力。

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来源期刊

ACS Applied Materials & Interfaces 工程技术-材料科学：综合

CiteScore

16.00

自引率

6.30%

发文量

4978

审稿时长

1.8 months

期刊介绍： ACS Applied Materials & Interfaces is a leading interdisciplinary journal that brings together chemists, engineers, physicists, and biologists to explore the development and utilization of newly-discovered materials and interfacial processes for specific applications. Our journal has experienced remarkable growth since its establishment in 2009, both in terms of the number of articles published and the impact of the research showcased. We are proud to foster a truly global community, with the majority of published articles originating from outside the United States, reflecting the rapid growth of applied research worldwide.