开发与 Tat 融合的药物结合蛋白,提高哺乳动物雷帕霉素靶点抑制剂的抗癌效果

IF 2.5 4区 生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Su Yeon Lim, Sugyeong Kim, Hongbin Kim, Hyun-Ouk Kim, Suk-Jin Ha, Kwang Suk Lim
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引用次数: 0

摘要

众所周知,哺乳动物雷帕霉素靶标(mTOR)可调控细胞生长、蛋白质稳定性和细胞周期进展,许多人类肿瘤都是由 mTOR 信号失调引起的。虽然目前已开发出多种 mTOR 抑制剂,但仍需要有效的递送系统来增强 mTOR 抑制剂的抗癌效果。在这项研究中,我们开发了 Tat 融合 mTOR 抑制剂结合域(Tat-MBD/TMBD),通过改善细胞内吸收来增强 mTOR 抑制剂的抗癌效果。TMBD/mTOR抑制剂复合物是MBD和mTOR抑制剂之间通过生物亲和力自发形成的,无需化学共轭和修饰。我们构建了一种由 Tat(蛋白质转导结构域)和 mTOR 抑制剂结合结构域(Tat-MBD)组成的重组融合蛋白表达载体来递送 mTOR 抑制剂。MBD 自发地与包括西罗莫司、依维莫司和替西罗莫司在内的 mTOR 抑制剂结合,形成 TMBD/mTOR 抑制剂复合物。实验证实,TMBD 可增强 mTOR 抑制剂在各种乳腺癌细胞中的递送效果,并提高抗癌疗效。我们证明了 mTOR 抑制剂的有效递送系统,无需对 mTOR 抑制剂进行化学共轭。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Development of Tat-fused drug binding protein to improve anti-cancer effect of mammalian target of rapamycin inhibitors

Development of Tat-fused drug binding protein to improve anti-cancer effect of mammalian target of rapamycin inhibitors

The mammalian target of rapamycin (mTOR) is known to regulate cell growth, protein stability and cell-cycle progression, and many human tumors result from the dysregulation of mTOR signaling. Although various mTOR inhibitors have been developed, effective delivery systems are still needed to enhance the anti-cancer effects of mTOR inhibitors. In this study, we developed the Tat-fused mTOR inhibitor binding domain (Tat-MBD/TMBD) for the enhancement of the anti-cancer effect of mTOR inhibitors, due to the improvement of intracellular uptake. A TMBD/mTOR inhibitors complex spontaneously formed by biological affinity between MBD and mTOR inhibitors without chemical conjugation and modification. We constructed that a recombinant fusion protein expression vector composed of Tat (protein transduction domain) and mTOR inhibitor-binding domain (Tat-MBD) to deliver the mTOR inhibitors. The MBD spontaneously bound with mTOR inhibitors including sirolimus, everolimus, and temsirolimus, resulting in the formation of a TMBD/mTOR inhibitors complex. The enhancement of the delivery efficacy of mTOR inhibitors into various breast cancer cells was confirmed and improved anti-cancer efficacy was observed. We demonstrated the effective delivery systems of mTOR inhibitors without chemical conjugation of mTOR inhibitors.

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来源期刊
Biotechnology and Bioprocess Engineering
Biotechnology and Bioprocess Engineering 工程技术-生物工程与应用微生物
CiteScore
5.00
自引率
12.50%
发文量
79
审稿时长
3 months
期刊介绍: Biotechnology and Bioprocess Engineering is an international bimonthly journal published by the Korean Society for Biotechnology and Bioengineering. BBE is devoted to the advancement in science and technology in the wide area of biotechnology, bioengineering, and (bio)medical engineering. This includes but is not limited to applied molecular and cell biology, engineered biocatalysis and biotransformation, metabolic engineering and systems biology, bioseparation and bioprocess engineering, cell culture technology, environmental and food biotechnology, pharmaceutics and biopharmaceutics, biomaterials engineering, nanobiotechnology, and biosensor and bioelectronics.
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