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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/64619/1/acsanm.8b00480.pdf
http://irep.iium.edu.my/64619/
https://pubs.acs.org/doi/pdf/10.1021/acsanm.8b00480
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spelling my.iium.irep.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
institution Universiti Islam Antarabangsa Malaysia
building IIUM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider International Islamic University Malaysia
content_source IIUM Repository (IREP)
url_provider http://irep.iium.edu.my/
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/64619/1/acsanm.8b00480.pdf
http://irep.iium.edu.my/64619/
https://pubs.acs.org/doi/pdf/10.1021/acsanm.8b00480
_version_ 1643617440907657216
score 13.222552

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