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新型磁性前药FeO@DOX的构建及其对肝癌的低毒性拮抗作用。

The construction of the novel magnetic prodrug FeO@DOX and its antagonistic effects on hepatocarcinoma with low toxicity.

作者信息

Li Jun, Li Liang, Lv Yang, Zou Hao, Wei Yanping, Nie Fei, Duan Wanli, Sedike Maidinamu, Xiao Liang, Wang Mei

机构信息

College of Traditional Chinese Medicine, Xinjiang Medical University Wulumuqi 830011 China

Faculty of Naval Medicine, Second Military Medical University (Naval Medical University) Shanghai 200433 China

出版信息

RSC Adv. 2020 Aug 5;10(48):28965-28974. doi: 10.1039/d0ra01729a. eCollection 2020 Aug 3.

Abstract

Doxorubicin (DOX) is widely used as a chemotherapeutic agent for liver cancer. However, its clinical applications are greatly restricted by its nonselective cytotoxicity. A novel magnetic prodrug, FeO@DOX, was designed, synthesized and characterized, and FeO and DOX were connected by the peptide CGGAAN. The magnetic prodrug FeO@DOX was successfully synthesized with average sizes of 95 nm and 322.5 nm by TEM (transmission electron microscopy) and Malvern Zetasizer instrument respectively. The maximum emission wavelength shifted from 594 nm for free DOX to 615 nm for conjugated DOX in the synthesized FeO@DOX. Both free DOX and FeO@DOX show strong cytotoxicity to legumain overexpressing PLC through apoptosis. Similarly, FeO@DOX and DOX equally reduced tumor volume and induced cell apoptosis in tumor tissues, while the former significantly maintained body weight and extended the life of nude mice, therefore serving as a promising nanocarrier for liver cancer treatment.

摘要

阿霉素(DOX)被广泛用作肝癌的化疗药物。然而,其非选择性细胞毒性极大地限制了其临床应用。设计、合成并表征了一种新型磁性前药FeO@DOX,FeO和DOX通过肽CGGAAN连接。通过透射电子显微镜(TEM)和马尔文Zetasizer仪器分别成功合成了平均尺寸为95 nm和322.5 nm的磁性前药FeO@DOX。合成的FeO@DOX中,最大发射波长从游离DOX的594 nm移至共轭DOX的615 nm。游离DOX和FeO@DOX均通过凋亡对过表达legumain的PLC表现出强烈的细胞毒性。同样,FeO@DOX和DOX同样减小了肿瘤体积并诱导肿瘤组织中的细胞凋亡,而前者显著维持了体重并延长了裸鼠的寿命,因此是一种有前景的肝癌治疗纳米载体。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c405/9055880/1f16fc82df77/d0ra01729a-f1.jpg

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