Mechanism Study of Thermally Induced Anti-Tumor Drug Loading to Engineered Human Heavy-Chain Ferritin Nanocages Aided by Computational Analysis
Diverse drug loading approaches for human heavy-chain ferritin (HFn), a promising drug nanocarrier, have been established. However, anti-tumor drug loading ratio and protein carrier recovery yield are bottlenecks for future clinical application. Mechanisms behind drug loading have not been elaborate...
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MDPI AG
2021-11-01
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| Series: | Biosensors |
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| Online Access: | https://www.mdpi.com/2079-6374/11/11/444 |
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| author | Shuang Yin Yongdong Liu Sheng Dai Bingyang Zhang Yiran Qu Yao Zhang Woo-Seok Choe Jingxiu Bi |
| author_facet | Shuang Yin Yongdong Liu Sheng Dai Bingyang Zhang Yiran Qu Yao Zhang Woo-Seok Choe Jingxiu Bi |
| author_sort | Shuang Yin |
| collection | DOAJ |
| description | Diverse drug loading approaches for human heavy-chain ferritin (HFn), a promising drug nanocarrier, have been established. However, anti-tumor drug loading ratio and protein carrier recovery yield are bottlenecks for future clinical application. Mechanisms behind drug loading have not been elaborated. In this work, a thermally induced drug loading approach was introduced to load anti-tumor drug doxorubicin hydrochloride (DOX) into HFn, and 2 functionalized HFns, HFn-PAS-RGDK, and HFn-PAS. Optimal conditions were obtained through orthogonal tests. All 3 HFn-based proteins achieved high protein recovery yield and drug loading ratio. Size exclusion chromatography (SEC) and transmission electron microscopy (TEM) results showed the majority of DOX loaded protein (protein/DOX) remained its nanocage conformation. Computational analysis, molecular docking followed by molecular dynamic (MD) simulation, revealed mechanisms of DOX loading and formation of by-product by investigating non-covalent interactions between DOX with HFn subunit and possible binding modes of DOX and HFn after drug loading. In in vitro tests, DOX in protein/DOX entered tumor cell nucleus and inhibited tumor cell growth. |
| first_indexed | 2024-03-10T05:40:14Z |
| format | Article |
| id | doaj.art-5ea83230122b408290251e6cbc31cf63 |
| institution | Directory Open Access Journal |
| issn | 2079-6374 |
| language | English |
| last_indexed | 2024-03-10T05:40:14Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biosensors |
| spelling | doaj.art-5ea83230122b408290251e6cbc31cf632023-11-22T22:36:15ZengMDPI AGBiosensors2079-63742021-11-01111144410.3390/bios11110444Mechanism Study of Thermally Induced Anti-Tumor Drug Loading to Engineered Human Heavy-Chain Ferritin Nanocages Aided by Computational AnalysisShuang Yin0Yongdong Liu1Sheng Dai2Bingyang Zhang3Yiran Qu4Yao Zhang5Woo-Seok Choe6Jingxiu Bi7School of Chemical Engineering and Advanced Materials, The University of Adelaide, Adelaide, SA 5005, AustraliaState Key Laboratory of Biochemistry Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, ChinaDepartment of Chemical Engineering, Brunel University London, London UB8 3PH, UKSchool of Chemical Engineering and Advanced Materials, The University of Adelaide, Adelaide, SA 5005, AustraliaSchool of Chemical Engineering and Advanced Materials, The University of Adelaide, Adelaide, SA 5005, AustraliaState Key Laboratory of Biochemistry Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, ChinaSchool of Chemical Engineering), Sungkyunkwan University (SKKU), Suwon 16419, KoreaSchool of Chemical Engineering and Advanced Materials, The University of Adelaide, Adelaide, SA 5005, AustraliaDiverse drug loading approaches for human heavy-chain ferritin (HFn), a promising drug nanocarrier, have been established. However, anti-tumor drug loading ratio and protein carrier recovery yield are bottlenecks for future clinical application. Mechanisms behind drug loading have not been elaborated. In this work, a thermally induced drug loading approach was introduced to load anti-tumor drug doxorubicin hydrochloride (DOX) into HFn, and 2 functionalized HFns, HFn-PAS-RGDK, and HFn-PAS. Optimal conditions were obtained through orthogonal tests. All 3 HFn-based proteins achieved high protein recovery yield and drug loading ratio. Size exclusion chromatography (SEC) and transmission electron microscopy (TEM) results showed the majority of DOX loaded protein (protein/DOX) remained its nanocage conformation. Computational analysis, molecular docking followed by molecular dynamic (MD) simulation, revealed mechanisms of DOX loading and formation of by-product by investigating non-covalent interactions between DOX with HFn subunit and possible binding modes of DOX and HFn after drug loading. In in vitro tests, DOX in protein/DOX entered tumor cell nucleus and inhibited tumor cell growth.https://www.mdpi.com/2079-6374/11/11/444ferritindrug deliverythermally induced drug loadingcomputational analysis |
| spellingShingle | Shuang Yin Yongdong Liu Sheng Dai Bingyang Zhang Yiran Qu Yao Zhang Woo-Seok Choe Jingxiu Bi Mechanism Study of Thermally Induced Anti-Tumor Drug Loading to Engineered Human Heavy-Chain Ferritin Nanocages Aided by Computational Analysis Biosensors ferritin drug delivery thermally induced drug loading computational analysis |
| title | Mechanism Study of Thermally Induced Anti-Tumor Drug Loading to Engineered Human Heavy-Chain Ferritin Nanocages Aided by Computational Analysis |
| title_full | Mechanism Study of Thermally Induced Anti-Tumor Drug Loading to Engineered Human Heavy-Chain Ferritin Nanocages Aided by Computational Analysis |
| title_fullStr | Mechanism Study of Thermally Induced Anti-Tumor Drug Loading to Engineered Human Heavy-Chain Ferritin Nanocages Aided by Computational Analysis |
| title_full_unstemmed | Mechanism Study of Thermally Induced Anti-Tumor Drug Loading to Engineered Human Heavy-Chain Ferritin Nanocages Aided by Computational Analysis |
| title_short | Mechanism Study of Thermally Induced Anti-Tumor Drug Loading to Engineered Human Heavy-Chain Ferritin Nanocages Aided by Computational Analysis |
| title_sort | mechanism study of thermally induced anti tumor drug loading to engineered human heavy chain ferritin nanocages aided by computational analysis |
| topic | ferritin drug delivery thermally induced drug loading computational analysis |
| url | https://www.mdpi.com/2079-6374/11/11/444 |
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