Engineered Human Heavy-Chain Ferritin with Half-Life Extension and Tumor Targeting by PAS and RGDK Peptide Functionalization

doi:10.3390/pharmaceutics13040521

	Engineered Human Heavy-Chain Ferritin with Half-Life Extension and Tumor Targeting by PAS and RGDK Peptide Functionalization
	Yin, Shuang 3; Wang, Yan 1; Zhang, Bingyang 3; Qu, Yiran 3; Liu, Yongdong 4; Dai, Sheng 2; Zhang, Yao 4; Wang, Yingli 1; Bi, Jingxiu 3
刊名	PHARMACEUTICS
	2021-04-01
卷号	13 期号:4 页码:16
关键词	ferritin drug delivery tumor targeting half-life extension
DOI	10.3390/pharmaceutics13040521
英文摘要	Ferritin, one of the most investigated protein nanocages, is considered as a promising drug carrier because of its advantageous stability and safety. However, its short half-life and undesirable tumor targeting ability has limited its usage in tumor treatment. In this work, two types of functional peptides, half-life extension peptide PAS, and tumor targeting peptide RGDK (Arg-Gly-Asp-Lys), are inserted to human heavy-chain ferritin (HFn) at C-terminal through flexible linkers with two distinct enzyme cleavable sites. Structural characterizations show both HFn and engineered HFns can assemble into nanoparticles but with different apparent hydrodynamic volumes and molecular weights. RGDK peptide enhanced the internalization efficiency of HFn and showed a significant increase of growth inhibition against 4T1 cell line in vitro. Pharmacokinetic study in vivo demonstrates PAS peptides extended ferritin half-life about 4.9 times in Sprague Dawley rats. RGDK peptides greatly enhanced drug accumulation in the tumor site rather than in other organs in biodistribution analysis. Drug loaded PAS-RGDK functionalized HFns curbed tumor growth with significantly greater efficacies in comparison with drug loaded HFn.
资助项目	University of Adelaide ; Institute of Process Engineering, Chinese Academy of Sciences ; National Natural Science Foundation of China[21576267] ; Beijing Natural Science Foundation[2162041] ; Shanxi Education Science "1331 project" special research project (Research and Development of Traditional Chinese Medicine Micro-emulsion and New Biological Preparation)
WOS关键词	ALBUMIN-BINDING DOMAIN ; CATHEPSIN-B ; NANOPARTICLES ; DELIVERY ; ENCAPSULATION ; SEQUENCE ; THERAPY
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	MDPI
WOS记录号	WOS:000643517100001
资助机构	University of Adelaide ; Institute of Process Engineering, Chinese Academy of Sciences ; National Natural Science Foundation of China ; Beijing Natural Science Foundation ; Shanxi Education Science "1331 project" special research project (Research and Development of Traditional Chinese Medicine Micro-emulsion and New Biological Preparation)
内容类型	期刊论文
源URL	[http://ir.ipe.ac.cn/handle/122111/48574]
专题	中国科学院过程工程研究所
通讯作者	Wang, Yingli; Bi, Jingxiu
作者单位	1.Shanxi Univ Tradit Chinese Med, Sch Chinese Med & Food Engn, Jinzhong 030619, Peoples R China 2.Brunel Univ London, Dept Chem Engn, Uxbridge UB8 3PH, Middx, England 3.Univ Adelaide, Sch Chem Engn & Adv Mat, Adelaide, SA 5005, Australia 4.Chinese Acad Sci, Inst Proc Engn, State Key Lab Biochem Engn, Beijing 100190, Peoples R China
推荐引用方式 GB/T 7714	Yin, Shuang,Wang, Yan,Zhang, Bingyang,et al. Engineered Human Heavy-Chain Ferritin with Half-Life Extension and Tumor Targeting by PAS and RGDK Peptide Functionalization[J]. PHARMACEUTICS,2021,13(4):16.
APA	Yin, Shuang.,Wang, Yan.,Zhang, Bingyang.,Qu, Yiran.,Liu, Yongdong.,...&Bi, Jingxiu.(2021).Engineered Human Heavy-Chain Ferritin with Half-Life Extension and Tumor Targeting by PAS and RGDK Peptide Functionalization.PHARMACEUTICS,13(4),16.
MLA	Yin, Shuang,et al."Engineered Human Heavy-Chain Ferritin with Half-Life Extension and Tumor Targeting by PAS and RGDK Peptide Functionalization".PHARMACEUTICS 13.4(2021):16.