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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Autores principales:	Shuang Yin, Yongdong Liu, Sheng Dai, Bingyang Zhang, Yiran Qu, Yao Zhang, Woo-Seok Choe, Jingxiu Bi
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	ferritin drug delivery thermally induced drug loading computational analysis Biotechnology TP248.13-248.65
Acceso en línea:	https://doaj.org/article/5ea83230122b408290251e6cbc31cf63
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spelling	oai:doaj.org-article:5ea83230122b408290251e6cbc31cf632021-11-25T16:55:29ZMechanism Study of Thermally Induced Anti-Tumor Drug Loading to Engineered Human Heavy-Chain Ferritin Nanocages Aided by Computational Analysis10.3390/bios111104442079-6374https://doaj.org/article/5ea83230122b408290251e6cbc31cf632021-11-01T00:00:00Zhttps://www.mdpi.com/2079-6374/11/11/444https://doaj.org/toc/2079-6374Diverse 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.Shuang YinYongdong LiuSheng DaiBingyang ZhangYiran QuYao ZhangWoo-Seok ChoeJingxiu BiMDPI AGarticleferritindrug deliverythermally induced drug loadingcomputational analysisBiotechnologyTP248.13-248.65ENBiosensors, Vol 11, Iss 444, p 444 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	ferritin drug delivery thermally induced drug loading computational analysis Biotechnology TP248.13-248.65
spellingShingle	ferritin drug delivery thermally induced drug loading computational analysis Biotechnology TP248.13-248.65 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
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.
format	article
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
title	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_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_sort	mechanism study of thermally induced anti-tumor drug loading to engineered human heavy-chain ferritin nanocages aided by computational analysis
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/5ea83230122b408290251e6cbc31cf63
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Mechanism Study of Thermally Induced Anti-Tumor Drug Loading to Engineered Human Heavy-Chain Ferritin Nanocages Aided by Computational Analysis

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