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姜黄素与半胱氨酸桥连肽共组装构建肿瘤响应性纳米胶束用于高效化疗。

Co-assembly of curcumin and a cystine bridged peptide to construct tumor-responsive nano-micelles for efficient chemotherapy.

机构信息

School of Chemical Engineering and Technology, State Key Laboratory of Chemical Engineering, Tianjin University, Tianjin 300350, P. R. China.

School of Medicine, Nankai University, Tianjin 300071, P. R. China.

出版信息

J Mater Chem B. 2020 Mar 4;8(9):1944-1951. doi: 10.1039/c9tb02625h.

Abstract

The effective uptake and release of hydrophobic antitumor drugs in cancer cells is a practical challenge for tumor chemotherapy. Many methods were developed to conquer it through modifying drug molecules with hydrophilic groups, or fabricating nanodrugs based on hydrophilic materials. In recent years, peptides have attracted significant interest as part of a promising platform for fabricating nanodrugs due to their low cytotoxicity, favorable variability and self-assembly property. In this study, a cystine bridged peptide (CBP) was designed to co-assemble with a hydrophobic antitumor drug curcumin (CCM), to form a tumor-responsive nanodrug. The hydrophilicity of the peptide promotes the water-dispersity of nanodrugs, and the disulfide bond in cystine, which is cleavable by glutathione (GSH), was involved considering the overexpressed GSH in tumor microenvironments. In vitro and in vivo tests on cervical cancer cells revealed that the obtained nanodrug can rapidly dissociate at tumor sites and inhibit the tumor growth with limited side effects on healthy tissues.

摘要

疏水性抗肿瘤药物在癌细胞中的有效摄取和释放是肿瘤化疗的一个实际挑战。许多方法被开发出来,通过用亲水基团修饰药物分子,或基于亲水材料制备纳米药物来克服这一问题。近年来,由于其低细胞毒性、良好的可变性和自组装特性,肽作为一种很有前途的纳米药物制备平台引起了人们的极大兴趣。在这项研究中,设计了一个半胱氨酸桥连肽(CBP)与疏水性抗肿瘤药物姜黄素(CCM)共组装,形成一种肿瘤响应性纳米药物。肽的亲水性促进了纳米药物的水分散性,并且考虑到肿瘤微环境中过表达的谷胱甘肽(GSH),半胱氨酸中的二硫键(可被 GSH 切割)被包含在内。对宫颈癌细胞的体外和体内试验表明,所得纳米药物可以在肿瘤部位迅速解离,并抑制肿瘤生长,对健康组织的副作用有限。

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