Efficient delivery of cytosolic proteins by protein-hexahistidine-metal co-assemblies

doi:10.1016/j.actbio.2021.05.001

科研成果详情

题名	Efficient delivery of cytosolic proteins by protein-hexahistidine-metal co-assemblies
作者	Huang, Wenjuan1,2; Zhou, Sijie2; Tang, Bojiao2; Xu, Hongyan2; Wu, Xiaoxiao 2; Li, Na 3; Zan, Xingjie2,3; Geng, Wujun4
发表日期	2021-06-15
发表期刊	ACTA BIOMATERIALIA 影响因子和分区
语种	英语
原始文献类型	Article
关键词	Protein delivery Intracellular delivery Coordination polymer Lysosomal escape Hexahistidine
其他关键词	INTRACELLULAR DELIVERY ; NANOPARTICLES ; STRATEGY ; SYSTEM ; ENZYME ; CELLS
摘要	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 His 6 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 His 6 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. (C) 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
资助项目	National Key RD Program [2017YFC1104602]; Wenzhou Institute of UCAS [WIUCASQD2019009]; Science and Technology Projects of Wenzhou [ZY202005, ZY2019015]; Natural Science Foundation of Zhejiang ProvinceNatural Science Foundation of Zhejiang Province [LQ21C100002]; Medical Science and Technology Project of Zhejiang Province [2020KY360]; Zhejiang public welfare technology research plan [LGD20H290002]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81774109, 81973620]
出版者	ELSEVIER SCI LTD
出版地	OXFORD
ISSN	1742-7061
EISSN	1878-7568
卷号	129 页码:199-208
DOI	10.1016/j.actbio.2021.05.001
页数	47
WOS类目	Engineering, Biomedical ; Materials Science, Biomaterials
WOS研究方向	Engineering ; Materials Science
WOS记录号	WOS:000671497100005
收录类别	SCIE ; PUBMED ; EI ; SCOPUS
EI入藏号	20215111338626
URL	查看原文
PubMed ID	33991683
SCOPUSEID	2-s2.0-85108549943
通讯作者地址	[Zan, Xingjie]School of Ophthalmology and Optometry,Eye Hospital,School of Biomedical Engineering,Wenzhou Medical University,Wenzhou,325035,China
Scopus学科分类	Biotechnology;Biomaterials;Biochemistry;Biomedical Engineering;Molecular Biology
TOP期刊	TOP期刊
引用统计	被引频次：1[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/5307
专题	其他_附属台州医院（浙江省台州医院）附属第一医院_麻醉科第一临床医学院（信息与工程学院）、附属第一医院_麻醉科
通讯作者	Zan, Xingjie
作者单位	1.Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University,Linhai,317000,China; 2.School of Ophthalmology and Optometry,Eye Hospital,School of Biomedical Engineering,Wenzhou Medical University,Wenzhou,325035,China; 3.Engineering Research Center of Clinical Functional Materials and Diagnosis & Treatment Devices of Zhejiang Province,Wenzhou Institute,University of Chinese Academy of Sciences,Wenzhou,325001,China; 4.Department of Anesthesiology,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,325000,China
第一作者单位	其他_附属台州医院（浙江省台州医院）
第一作者的第一单位	其他_附属台州医院（浙江省台州医院）
推荐引用方式 GB/T 7714	Huang, Wenjuan,Zhou, Sijie,Tang, Bojiao,et al. Efficient delivery of cytosolic proteins by protein-hexahistidine-metal co-assemblies[J]. ACTA BIOMATERIALIA,2021,129:199-208.
APA	Huang, Wenjuan., Zhou, Sijie., Tang, Bojiao., Xu, Hongyan., Wu, Xiaoxiao., ... & Geng, Wujun. (2021). Efficient delivery of cytosolic proteins by protein-hexahistidine-metal co-assemblies. ACTA BIOMATERIALIA, 129, 199-208.
MLA	Huang, Wenjuan,et al."Efficient delivery of cytosolic proteins by protein-hexahistidine-metal co-assemblies".ACTA BIOMATERIALIA 129(2021):199-208.