Efficient Delivery of Cytosolic Proteins by Protein-Hexahistidine-Metal Co-Assemblies

Wenjuan Huang, Sijie Zhou, B. Tang, Hongyan Xu, Xiaoxiao Wu, Na Li, Xingjie Zan, W. Geng
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引用次数: 6

Abstract

Proteins play key roles in most biological processes, and protein dysfunction can cause various diseases. Over the past few decades, tremendous development has occurred in the protein therapeutic market due to the high specificity, low side effects, and low risk of proteins. Currently, all protein drugs on the market are based on extracellular targeting; more than 70% of intracellular targets remain un-druggable. Efficient delivery of cytosolic proteins is of significance for protein drugs, advanced biotechnology and molecular cell biology. Herein, we developed a co-assembly strategy for protein-hexahistidine-metal for intracellular protein delivery. Based on the coordinative interaction between His6 and metal ions, various proteins were encapsulated in situ into nanosized and positively charged protein encapsulation particles(Protein@HmA) through a co-assembly process with a high loading capacity and loading efficiency. Protein@HmA was able to deliver proteins with diverse physicochemical properties through multiple endocytosis pathways, and the protein could quickly escape from endosomes. In addition, the bioactivity of the loaded protein during co-assembly and the intracellular delivery processes were well preserved and could be properly exerted inside cells. Our results demonstrate that this strategy should be a valuable platform for protein delivery and has huge potential in protein-based theranostics. STATEMENT OF SIGNIFICANCE: : Intracellular targets with protein drugs may provide a new way for the treatment of many refractory disease. Herein, we developed a co-assembly strategy for protein-hexahistidine-metal for efficient intracellular protein delivery. Based on the coordinative interaction between His6 and metal ions, various proteins were encapsulated in situ into nanosized and positively charged particles (Protein@HmA) with a high loading efficiency. Protein@HmA was able to deliver different proteins through multiple endocytosis pathways, and the protein could quickly escape from endosomes. In addition, the bioactivity of the loaded protein during co-assembly and the intracellular delivery processes were well preserved and could be properly exerted inside cells. This strategy should be a valuable platform for protein delivery and has huge potential in protein-based theranostics.
蛋白质-六组氨酸-金属共聚体有效递送细胞质蛋白
蛋白质在大多数生物过程中起着关键作用,蛋白质功能障碍可导致多种疾病。在过去的几十年里,由于蛋白质具有高特异性、低副作用、低风险的特点,蛋白质治疗市场得到了巨大的发展。目前,市场上所有的蛋白质药物都是基于细胞外靶向;超过70%的细胞内靶点仍然是不可药物治疗的。胞质蛋白的高效递送对蛋白质药物、先进生物技术和分子细胞生物学具有重要意义。在此,我们开发了一种用于细胞内蛋白质递送的蛋白质-六组氨酸-金属共组装策略。基于His6与金属离子的协同作用,通过共组装工艺将多种蛋白质原位封装成纳米级带正电的蛋白质封装颗粒(Protein@HmA),具有较高的负载能力和负载效率。Protein@HmA能够通过多种内吞作用途径传递具有多种物理化学性质的蛋白质,并且蛋白质可以快速从内体中逃逸。此外,负载蛋白在共组装和细胞内递送过程中的生物活性得到了很好的保存,可以在细胞内适当地发挥作用。我们的研究结果表明,这种策略应该是一个有价值的蛋白质递送平台,在基于蛋白质的治疗中具有巨大的潜力。意义说明:细胞内靶向蛋白药物可能为许多难治性疾病的治疗提供新的途径。在此,我们开发了一种蛋白质-六组氨酸-金属的共组装策略,用于有效的细胞内蛋白质递送。基于His6与金属离子的协同作用,各种蛋白质被原位封装成纳米级正电荷粒子(Protein@HmA),负载效率高。Protein@HmA能够通过多种内吞作用途径传递不同的蛋白质,并且蛋白质可以快速地从内体中逃逸。此外,负载蛋白在共组装和细胞内递送过程中的生物活性得到了很好的保存,可以在细胞内适当地发挥作用。这种策略应该是一个有价值的蛋白质递送平台,在基于蛋白质的治疗中具有巨大的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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