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HepG2细胞同源递送阿霉素的抗肝癌作用

Anti-hepatoma effect of homologous delivery of doxorubicin by HepG2 cells.

作者信息

Sun Lina, Ma Baonan, Yang Fangzhou, Zou Hang, Guo Yifei, Wang Xiangtao, Han Meihua

机构信息

Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China; School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, China.

Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China.

出版信息

Int J Pharm. 2025 Feb 10;670:125113. doi: 10.1016/j.ijpharm.2024.125113. Epub 2024 Dec 20.

Abstract

Compared to conventional polymer-based and biomaterial carriers, cells as vehicles for delivering bioactive molecules in the treatment of tumor diseases offer characteristics such as non-toxicity, biocompatibility, low immunogenicity, and prolonged in vivo circulation. However, the focus of current cell drug delivery systems predominantly lies on live cells, such as red blood cells, white blood cells and others. Here, a drug delivery strategy targeting liver cancer utilizing cryo-shocked liver cancer cells (HepG2) as carriers was presented, and non-proliferative HepG2 cells particles loaded with DOX (HepG2-DOX) was effectively prepared, which has good homologous targeting. Subsequent in vitro and in vivo experiments demonstrated the non-proliferative and non-pathogenic nature of this drug delivery system. The outcomes of in vitro experiments revealed that the inhibitory effect of HepG2-DOX on HepG2 was approximately five times higher than that of free DOX, with the IC value of HepG2-DOX being 0.0739 µg/mL and free DOX being 0.3606 µg/mL. Furthermore, in comparison to the positive DOX group, the HepG2-DOX group has a very significant advantage in tumor inhibition rate (91.34 % vs. 64.20 %). Cell uptake experiments indicated significant HepG2-DOX uptake by HepG2 cells compared to 4T1, LO2, and Raw cell groups, highlighting the excellent cell specificity of HepG2-DOX. Fluorescence imaging conducted in mice following the administration of HepG2-DOX demonstrated prompt drug localization within the tumor region, highlighting exceptional in vivo targeting precision. To sum up, this study introduced a novel strategy utilizing cryo-shocked liver cancer cells as a drug delivery system, effectively treating liver tumor by enhancing tumor targeting specificity.

摘要

与传统的基于聚合物的生物材料载体相比,细胞作为在肿瘤疾病治疗中递送生物活性分子的载体,具有无毒、生物相容性好、免疫原性低和体内循环时间长等特点。然而,目前细胞药物递送系统的重点主要在于活细胞,如红细胞、白细胞等。在此,提出了一种利用冷冻休克肝癌细胞(HepG2)作为载体靶向肝癌的药物递送策略,并有效制备了负载阿霉素的非增殖性HepG2细胞颗粒(HepG2-DOX),其具有良好的同源靶向性。随后的体外和体内实验证明了该药物递送系统的非增殖性和无致病性。体外实验结果表明,HepG2-DOX对HepG2的抑制作用比游离阿霉素高约5倍,HepG2-DOX的IC值为0.0739μg/mL,游离阿霉素为0.3606μg/mL。此外,与阳性阿霉素组相比,HepG2-DOX组在肿瘤抑制率方面具有非常显著的优势(91.34%对64.20%)。细胞摄取实验表明,与4T1、LO2和Raw细胞组相比,HepG2细胞对HepG2-DOX的摄取显著,突出了HepG2-DOX优异的细胞特异性。给小鼠注射HepG2-DOX后进行的荧光成像显示药物迅速定位在肿瘤区域,突出了其卓越的体内靶向精度。综上所述,本研究引入了一种利用冷冻休克肝癌细胞作为药物递送系统的新策略,通过提高肿瘤靶向特异性有效治疗肝肿瘤。

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