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Article

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

1
School of Chemical Engineering and Advanced Materials, The University of Adelaide, Adelaide SA5005, Australia
2
School of Chinese Medicine and Food Engineering, Shanxi University of Traditional Chinese Medicine, Jinzhong 030619, China
3
State Key Laboratory of Biochemistry Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China
4
Department of Chemical Engineering, Brunel University London, Uxbridge UB8 3PH, UK
*
Authors to whom correspondence should be addressed.
Academic Editors: Francisco José Ostos, José Antonio Lebrón, Pilar López-Cornejo and Patrick J. Sinko
Pharmaceutics 2021, 13(4), 521; https://doi.org/10.3390/pharmaceutics13040521
Received: 24 February 2021 / Revised: 24 March 2021 / Accepted: 6 April 2021 / Published: 9 April 2021
(This article belongs to the Special Issue Supramolecular Systems for Gene and Drug Delivery)
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. View Full-Text
Keywords: ferritin; drug delivery; tumor targeting; half-life extension ferritin; drug delivery; tumor targeting; half-life extension
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MDPI and ACS Style

Yin, S.; Wang, Y.; Zhang, B.; Qu, Y.; Liu, Y.; Dai, S.; Zhang, Y.; Wang, Y.; Bi, J. Engineered Human Heavy-Chain Ferritin with Half-Life Extension and Tumor Targeting by PAS and RGDK Peptide Functionalization. Pharmaceutics 2021, 13, 521. https://doi.org/10.3390/pharmaceutics13040521

AMA Style

Yin S, Wang Y, Zhang B, Qu Y, Liu Y, Dai S, Zhang Y, Wang Y, Bi J. Engineered Human Heavy-Chain Ferritin with Half-Life Extension and Tumor Targeting by PAS and RGDK Peptide Functionalization. Pharmaceutics. 2021; 13(4):521. https://doi.org/10.3390/pharmaceutics13040521

Chicago/Turabian Style

Yin, Shuang, Yan Wang, Bingyang Zhang, Yiran Qu, Yongdong Liu, Sheng Dai, Yao Zhang, Yingli Wang, and Jingxiu Bi. 2021. "Engineered Human Heavy-Chain Ferritin with Half-Life Extension and Tumor Targeting by PAS and RGDK Peptide Functionalization" Pharmaceutics 13, no. 4: 521. https://doi.org/10.3390/pharmaceutics13040521

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