Engineered Human Heavy-Chain Ferritin with Half-Life Extension and Tumor Targeting by PAS and RGDK Peptide Functionalization
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 p...
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MDPI AG
2021-04-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/13/4/521 |
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| author | Shuang Yin Yan Wang Bingyang Zhang Yiran Qu Yongdong Liu Sheng Dai Yao Zhang Yingli Wang Jingxiu Bi |
| author_facet | Shuang Yin Yan Wang Bingyang Zhang Yiran Qu Yongdong Liu Sheng Dai Yao Zhang Yingli Wang Jingxiu Bi |
| author_sort | Shuang Yin |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T12:28:22Z |
| format | Article |
| id | doaj.art-c9ac1fed0f614d66a04a7ceb3905eb98 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T12:28:22Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-c9ac1fed0f614d66a04a7ceb3905eb982023-11-21T14:54:10ZengMDPI AGPharmaceutics1999-49232021-04-0113452110.3390/pharmaceutics13040521Engineered Human Heavy-Chain Ferritin with Half-Life Extension and Tumor Targeting by PAS and RGDK Peptide FunctionalizationShuang Yin0Yan Wang1Bingyang Zhang2Yiran Qu3Yongdong Liu4Sheng Dai5Yao Zhang6Yingli Wang7Jingxiu Bi8School of Chemical Engineering and Advanced Materials, The University of Adelaide, Adelaide SA5005, AustraliaSchool of Chinese Medicine and Food Engineering, Shanxi University of Traditional Chinese Medicine, Jinzhong 030619, ChinaSchool of Chemical Engineering and Advanced Materials, The University of Adelaide, Adelaide SA5005, AustraliaSchool of Chemical Engineering and Advanced Materials, The University of Adelaide, Adelaide SA5005, AustraliaState Key Laboratory of Biochemistry Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, ChinaDepartment of Chemical Engineering, Brunel University London, Uxbridge UB8 3PH, UKState Key Laboratory of Biochemistry Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, ChinaSchool of Chinese Medicine and Food Engineering, Shanxi University of Traditional Chinese Medicine, Jinzhong 030619, ChinaSchool of Chemical Engineering and Advanced Materials, The University of Adelaide, Adelaide SA5005, AustraliaFerritin, 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.https://www.mdpi.com/1999-4923/13/4/521ferritindrug deliverytumor targetinghalf-life extension |
| spellingShingle | Shuang Yin Yan Wang Bingyang Zhang Yiran Qu Yongdong Liu Sheng Dai Yao Zhang Yingli Wang Jingxiu Bi Engineered Human Heavy-Chain Ferritin with Half-Life Extension and Tumor Targeting by PAS and RGDK Peptide Functionalization Pharmaceutics ferritin drug delivery tumor targeting half-life extension |
| title | Engineered Human Heavy-Chain Ferritin with Half-Life Extension and Tumor Targeting by PAS and RGDK Peptide Functionalization |
| title_full | Engineered Human Heavy-Chain Ferritin with Half-Life Extension and Tumor Targeting by PAS and RGDK Peptide Functionalization |
| title_fullStr | Engineered Human Heavy-Chain Ferritin with Half-Life Extension and Tumor Targeting by PAS and RGDK Peptide Functionalization |
| title_full_unstemmed | Engineered Human Heavy-Chain Ferritin with Half-Life Extension and Tumor Targeting by PAS and RGDK Peptide Functionalization |
| title_short | Engineered Human Heavy-Chain Ferritin with Half-Life Extension and Tumor Targeting by PAS and RGDK Peptide Functionalization |
| title_sort | engineered human heavy chain ferritin with half life extension and tumor targeting by pas and rgdk peptide functionalization |
| topic | ferritin drug delivery tumor targeting half-life extension |
| url | https://www.mdpi.com/1999-4923/13/4/521 |
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