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Title: | Mechanism Study of Thermally Induced Anti-Tumor Drug Loading to Engineered Human Heavy-Chain Ferritin Nanocages Aided by Computational Analysis |
Authors: | Yin, S Liu, Y Dai, S Zhang, B Qu, Y Zhang, Y Choe, W-S Bi, J |
Keywords: | ferritin;drug delivery;thermally induced drug loading;computational analysis |
Issue Date: | 11-Nov-2021 |
Publisher: | MDPI |
Citation: | Yin, S. et al. (2021) ‘Mechanism Study of Thermally Induced Anti-Tumor Drug Loading to Engineered Human Heavy-Chain Ferritin Nanocages Aided by Computational Analysis’, Biosensors, 11 (11), 444, pp. 1 - 17. doi: 10.3390/bios11110444. |
Abstract: | 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. |
Description: | Data Availability Statement: The data presented in this study are available on request from the corresponding author. Supplementary Materials are available online at: https://doi.org/10.3390/bios11110444 . |
URI: | https://bura.brunel.ac.uk/handle/2438/23506 |
DOI: | https://doi.org/10.3390/bios11110444 |
Other Identifiers: | ORCiD: Sheng Dai https://orcid.org/0000-0002-9152-0786 ORCiD: Yao Zhang https://orcid.org/0000-0002-0776-1764 444 |
Appears in Collections: | Dept of Chemical Engineering Research Papers |
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