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奥曲肽修饰的姜黄素联合多西他赛胶束的制备及体内特性考察

Development and characterization of octreotide-modified curcumin plus docetaxel micelles for potential treatment of non-small-cell lung cancer.

机构信息

Technology Research and Development Centre, Yunnan Baiyao Group Health Products Co., LTD , Kunming , China.

School of Pharmacy, Shandong University of Traditional Chinese Medicine , Jinan , China.

出版信息

Pharm Dev Technol. 2019 Nov;24(9):1164-1174. doi: 10.1080/10837450.2019.1647236. Epub 2019 Aug 8.

Abstract

We prepared octreotide (OCT)-modified curcumin plus docetaxel micelles to enhance active targeting and inhibit tumor metastasis by destroying vasculogenic mimicry (VM) channels. Soluplus was applied as an amphiphilic material to form micelles via film dispersion. The cytotoxic effects, active cellular targeting, and inhibitory effects on metastasis were systematically evaluated using A549 cells, and antitumor effects were evaluated using xenograft tumor-bearing mice. assays indicated that the OCT-modified curcumin plus docetaxel micelles showed robust cytotoxicity on A549 cells and effectively inhibited VM channels and tumor metastasis. Studying the mechanism of action indicated that OCT-modified curcumin plus docetaxel micelles downregulated MMP-2 and HIF-1α. assays indicated that OCT-modified curcumin plus docetaxel micelles increased drug accumulation at tumor sites and showed obvious antitumor efficacy. The developed OCT-modified curcumin plus docetaxel micelles may offer a promising treatment strategy for non-small-cell lung cancer.

摘要

我们制备了奥曲肽(OCT)修饰的姜黄素联合多西紫杉醇胶束,通过破坏血管生成拟态(VM)通道来增强主动靶向和抑制肿瘤转移。Soluplus 被用作两亲材料,通过薄膜分散形成胶束。使用 A549 细胞系统地评估了细胞毒性作用、主动细胞靶向和对转移的抑制作用,并使用荷瘤小鼠评估了抗肿瘤作用。实验表明,奥曲肽修饰的姜黄素联合多西紫杉醇胶束对 A549 细胞具有较强的细胞毒性,并能有效抑制 VM 通道和肿瘤转移。作用机制研究表明,奥曲肽修饰的姜黄素联合多西紫杉醇胶束下调 MMP-2 和 HIF-1α。体内实验表明,奥曲肽修饰的姜黄素联合多西紫杉醇胶束增加了肿瘤部位的药物蓄积,并显示出明显的抗肿瘤疗效。开发的奥曲肽修饰的姜黄素联合多西紫杉醇胶束可能为非小细胞肺癌提供了一种有前途的治疗策略。

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