磁性驱动的纳米转运蛋白辅助的细胞内递送和蛋白质的自主释放。,ACS Applied Materials & Interfaces

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磁性驱动的纳米转运蛋白辅助的细胞内递送和蛋白质的自主释放。
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2020-08-19 , DOI: 10.1021/acsami.0c12249
Gong Cheng ₁ , Xiaohui Han ₁ , Si-Yang Zheng _{1,

2}

Affiliation

生物功能蛋白（例如活性酶和治疗性蛋白）在疾病治疗中显示出巨大的希望。然而，由于蛋白质的降解和变性脆弱性以及各种生物屏障的存在（例如膜转运效率低），使得蛋白质的细胞内递送面临着巨大的挑战。在这里，我们报告了磁性驱动和氧化还原响应的纳米转运蛋白（MRNT）的生物功能蛋白的高效细胞内传递。与没有纳米级货舱的MRNT相比，MRNT的货物容量非常高。我们已经使用纳米粒子跟踪分析和磁驱动评估来证明MRNT的方向性和动态运动。此外，活性MRNT可以转移到细胞质中，并感觉到还原的胞质环境以自动释放蛋白质货物。已经使用胞吞抑制剂研究了MRNT的内在化机理。在磁力驱动下，MRNT可以促进95％以上的蛋白质转导效率，并且活性MRNT的细胞内蛋白质递送显示出比静态酶更高的（约4倍）酶活性和治疗效率。我们的概念验证研究为细胞内蛋白质转导提供了有价值的工具，并为生物技术和蛋白质治疗做出了贡献。MRNT可以促进95％以上的蛋白质转导效率，而活性MRNT的细胞内蛋白质递送显示出比静态酶更高的（约4倍）酶活性和治疗效率。我们的概念验证研究为细胞内蛋白质转导提供了有价值的工具，并为生物技术和蛋白质治疗做出了贡献。MRNT可以促进95％以上的蛋白质转导效率，而活性MRNT的细胞内蛋白质递送显示出比静态酶更高的（约4倍）酶活性和治疗效率。我们的概念验证研究为细胞内蛋白质转导提供了有价值的工具，并为生物技术和蛋白质治疗做出了贡献。

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Magnetically Driven Nanotransporter-Assisted Intracellular Delivery and Autonomous Release of Proteins.

Biofunctional proteins such as active enzymes and therapeutic proteins show tremendous promise in disease treatment. However, intracellular delivery of proteins is facing substantial challenges owing to their vulnerability to degradation and denaturation and the presence of various biological barriers such as their low membrane transport efficiency. Herein, we report a magnetically driven and redox-responsive nanotransporter (MRNT) for highly efficient intracellular delivery of biofunctional proteins. The MRNT has remarkably high cargo capacity, compared with that without nanoscale cargo compartments. We have demonstrated the directional and dynamic motion of the MRNT using both nanoparticle tracking analysis and magnetic driving evaluation. Moreover, the active MRNT can translocate into the cytosol and sense the reducing cytosolic environment to discharge protein cargoes autonomously. The internalization mechanism of the MRNT has been studied using endocytosis inhibitors. Under the magnetic drive, the MRNT can promote a protein transduction efficiency of over 95%, and the intracellular protein delivery by the active MRNT shows significantly higher (∼4 times) enzymatic activity and therapeutic efficiency than those achieved by the static ones. Our proof-of-concept study provides a valuable tool for intracellular protein transduction and contributes to biotechnology and protein therapeutics.

更新日期：2020-09-16

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