Engineering human epidermal growth receptor 2‑Targeting hepatitis B virus core nanoparticles for siRNA delivery in vitro and in vivo

Hepatitis B virus core (HBc) particles acquire the capacity to disassemble and reassemble in a controlled manner, allowing entrapment and delivery of drugs and macromolecules to cells. HBc particles are made of 180−240 copies of 21 kDa protein monomers, assembled into 30−34 nm diameter icosahedral...

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Main Authors:	Mohamed Suffian, Izzat Fahimuddin, Wang, Julie Tzu-Wen, Faruqu, Farid Nazer, Benitez, Julio, Nishimura, Yuya, Ogino, Chiaki, Akihiko, Kondo, Al-Jamal, Khuloud
Format:	Article
Language:	English
Published:	American Chemical Society 2018
Subjects:	RM147 Administration of Drugs and Other Therapeutic Agents RM300 Drugs and their action
Online Access:	http://irep.iium.edu.my/64619/ http://irep.iium.edu.my/64619/ http://irep.iium.edu.my/64619/1/acsanm.8b00480.pdf

id	iium-64619
recordtype	eprints
spelling	iium-646192018-07-26T07:53:40Z http://irep.iium.edu.my/64619/ Engineering human epidermal growth receptor 2‑Targeting hepatitis B virus core nanoparticles for siRNA delivery in vitro and in vivo Mohamed Suffian, Izzat Fahimuddin Wang, Julie Tzu-Wen Faruqu, Farid Nazer Benitez, Julio Nishimura, Yuya Ogino, Chiaki Akihiko, Kondo Al-Jamal, Khuloud RM147 Administration of Drugs and Other Therapeutic Agents RM300 Drugs and their action Hepatitis B virus core (HBc) particles acquire the capacity to disassemble and reassemble in a controlled manner, allowing entrapment and delivery of drugs and macromolecules to cells. HBc particles are made of 180−240 copies of 21 kDa protein monomers, assembled into 30−34 nm diameter icosahedral particles. In this study, we aimed at formulating HBc particles for the delivery of siRNA for gene silencing in vitro and in vivo. We have previously reported recombinant HBc particles expressing ZHER2 affibodies, specifically targeting human epidermal growth receptor 2 (HER2)-expressing cancer cells (ZHER2-ΔHBc). siRNA was encapsulated within the ZHER2-ΔHBc particles following disassembly and reassembly. The ZHER2-ΔHBc−siRNA hybrids were able to secure the encapsulated siRNA from serum and nucleases in vitro. Enhanced siRNA uptake in HER2-expressing cancer cells treated with ZHER2-ΔHBc−siRNA hybrids was observed compared to the nontargeted HBc−siRNA hybrids in a time- and dose-dependent manner. A successful in vitro pololike kinase 1 (PLK1) gene knockdown was demonstrated in cancer cells treated with ZHER2-ΔHBc−siPLK1 hybrids, to levels comparable to commercial transfecting reagents. Interestingly, ZHER2-ΔHBc particles exhibit intrinsic capability of reducing the solid tumor mass, independent of siPLK1 therapy, in an intraperitoneal tumor model following intraperitoneal injection. American Chemical Society 2018 Article NonPeerReviewed application/pdf en http://irep.iium.edu.my/64619/1/acsanm.8b00480.pdf Mohamed Suffian, Izzat Fahimuddin and Wang, Julie Tzu-Wen and Faruqu, Farid Nazer and Benitez, Julio and Nishimura, Yuya and Ogino, Chiaki and Akihiko, Kondo and Al-Jamal, Khuloud (2018) Engineering human epidermal growth receptor 2‑Targeting hepatitis B virus core nanoparticles for siRNA delivery in vitro and in vivo. ACS Applied Nano Materials, xx (xx). pp. 1-14. ISSN 2574-0970 (In Press) https://pubs.acs.org/doi/pdf/10.1021/acsanm.8b00480
repository_type	Digital Repository
institution_category	Local University
institution	International Islamic University Malaysia
building	IIUM Repository
collection	Online Access
language	English
topic	RM147 Administration of Drugs and Other Therapeutic Agents RM300 Drugs and their action
spellingShingle	RM147 Administration of Drugs and Other Therapeutic Agents RM300 Drugs and their action Mohamed Suffian, Izzat Fahimuddin Wang, Julie Tzu-Wen Faruqu, Farid Nazer Benitez, Julio Nishimura, Yuya Ogino, Chiaki Akihiko, Kondo Al-Jamal, Khuloud Engineering human epidermal growth receptor 2‑Targeting hepatitis B virus core nanoparticles for siRNA delivery in vitro and in vivo
description	Hepatitis B virus core (HBc) particles acquire the capacity to disassemble and reassemble in a controlled manner, allowing entrapment and delivery of drugs and macromolecules to cells. HBc particles are made of 180−240 copies of 21 kDa protein monomers, assembled into 30−34 nm diameter icosahedral particles. In this study, we aimed at formulating HBc particles for the delivery of siRNA for gene silencing in vitro and in vivo. We have previously reported recombinant HBc particles expressing ZHER2 affibodies, specifically targeting human epidermal growth receptor 2 (HER2)-expressing cancer cells (ZHER2-ΔHBc). siRNA was encapsulated within the ZHER2-ΔHBc particles following disassembly and reassembly. The ZHER2-ΔHBc−siRNA hybrids were able to secure the encapsulated siRNA from serum and nucleases in vitro. Enhanced siRNA uptake in HER2-expressing cancer cells treated with ZHER2-ΔHBc−siRNA hybrids was observed compared to the nontargeted HBc−siRNA hybrids in a time- and dose-dependent manner. A successful in vitro pololike kinase 1 (PLK1) gene knockdown was demonstrated in cancer cells treated with ZHER2-ΔHBc−siPLK1 hybrids, to levels comparable to commercial transfecting reagents. Interestingly, ZHER2-ΔHBc particles exhibit intrinsic capability of reducing the solid tumor mass, independent of siPLK1 therapy, in an intraperitoneal tumor model following intraperitoneal injection.
format	Article
author	Mohamed Suffian, Izzat Fahimuddin Wang, Julie Tzu-Wen Faruqu, Farid Nazer Benitez, Julio Nishimura, Yuya Ogino, Chiaki Akihiko, Kondo Al-Jamal, Khuloud
author_facet	Mohamed Suffian, Izzat Fahimuddin Wang, Julie Tzu-Wen Faruqu, Farid Nazer Benitez, Julio Nishimura, Yuya Ogino, Chiaki Akihiko, Kondo Al-Jamal, Khuloud
author_sort	Mohamed Suffian, Izzat Fahimuddin
title	Engineering human epidermal growth receptor 2‑Targeting hepatitis B virus core nanoparticles for siRNA delivery in vitro and in vivo
title_short	Engineering human epidermal growth receptor 2‑Targeting hepatitis B virus core nanoparticles for siRNA delivery in vitro and in vivo
title_full	Engineering human epidermal growth receptor 2‑Targeting hepatitis B virus core nanoparticles for siRNA delivery in vitro and in vivo
title_fullStr	Engineering human epidermal growth receptor 2‑Targeting hepatitis B virus core nanoparticles for siRNA delivery in vitro and in vivo
title_full_unstemmed	Engineering human epidermal growth receptor 2‑Targeting hepatitis B virus core nanoparticles for siRNA delivery in vitro and in vivo
title_sort	engineering human epidermal growth receptor 2‑targeting hepatitis b virus core nanoparticles for sirna delivery in vitro and in vivo
publisher	American Chemical Society
publishDate	2018
url	http://irep.iium.edu.my/64619/ http://irep.iium.edu.my/64619/ http://irep.iium.edu.my/64619/1/acsanm.8b00480.pdf
first_indexed	2023-09-18T21:31:42Z
last_indexed	2023-09-18T21:31:42Z
_version_	1777412554015899648

Engineering human epidermal growth receptor 2‑Targeting hepatitis B virus core nanoparticles for siRNA delivery in vitro and in vivo

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