Please use this identifier to cite or link to this item: http://bura.brunel.ac.uk/handle/2438/22968
Title: Engineered human heavy-chain ferritin with half-life extension and tumor targeting by PAS and RGDK peptide functionalization
Authors: Yin, S
Wang, Y
Zhang, B
Qu, Y
Liu, Y
Dai, S
Zhang, Y
Wang, Y
Bi, J
Keywords: ferritin;drug delivery;tumor targeting;half-life extension
Issue Date: 9-Apr-2021
Publisher: MDPI
Citation: Yin, S., Wang, Yan, Zhang, B., Qu, Y., Liu, Y., Dai, S., Zhang, Y., Wang, Yingli and Bi, J. (2021) ‘Engineered Human Heavy-Chain Ferritin with Half-Life Extension and Tumor Targeting by PAS and RGDK Peptide Functionalization’, Pharmaceutics. MDPI AG, 13(4), p. 521. doi: 10.3390/pharmaceutics13040521.
Abstract: 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.
URI: http://bura.brunel.ac.uk/handle/2438/22968
DOI: http://dx.doi.org/10.3390/pharmaceutics13040521
ISSN: 1999-4923
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