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Engineered Human Heavy-Chain Ferritin with Half-Life Extension and Tumor Targeting by PAS and RGDK Peptide Functionalization
Yin, Shuang1; Wang, Yan2; Zhang, Bingyang1; Qu, Yiran1; Liu, Yongdong3; Dai, Sheng4; Zhang, Yao3; Wang, Yingli2; Bi, Jingxiu1
2021-04-01
Source PublicationPHARMACEUTICS
Volume13Issue:4Pages:16
AbstractFerritin, 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.
Keywordferritin drug delivery tumor targeting half-life extension
DOI10.3390/pharmaceutics13040521
Language英语
WOS KeywordALBUMIN-BINDING DOMAIN ; CATHEPSIN-B ; NANOPARTICLES ; DELIVERY ; ENCAPSULATION ; SEQUENCE ; THERAPY
Funding ProjectUniversity 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 Research AreaPharmacology & Pharmacy
WOS SubjectPharmacology & Pharmacy
Funding OrganizationUniversity 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)
WOS IDWOS:000643517100001
PublisherMDPI
Citation statistics
Document Type期刊论文
Identifierhttp://ir.ipe.ac.cn/handle/122111/48575
Collection中国科学院过程工程研究所
Corresponding AuthorWang, Yingli; Bi, Jingxiu
Affiliation1.Univ Adelaide, Sch Chem Engn & Adv Mat, Adelaide, SA 5005, Australia
2.Shanxi Univ Tradit Chinese Med, Sch Chinese Med & Food Engn, Jinzhong 030619, Peoples R China
3.Chinese Acad Sci, Inst Proc Engn, State Key Lab Biochem Engn, Beijing 100190, Peoples R China
4.Brunel Univ London, Dept Chem Engn, Uxbridge UB8 3PH, Middx, England
Recommended Citation
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.
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