A Simple Add-and-Display Method for Immobilisation of Cancer Drug on His-tagged Virus-like Nanoparticles for Controlled Drug Delivery

Abstract pH-responsive virus-like nanoparticles (VLNPs) hold promising potential as drug delivery systems for cancer therapy. In the present study, hepatitis B virus (HBV) VLNPs harbouring His-tags were used to display doxorubicin (DOX) via nitrilotriacetic acid (NTA) conjugation. The His-tags serve...

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Main Authors: Roya Biabanikhankahdani, Saadi Bayat, Kok Lian Ho, Noorjahan Banu Mohamed Alitheen, Wen Siang Tan
Format: Article
Language:English
Published: Nature Portfolio 2017-07-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-017-05525-4
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author Roya Biabanikhankahdani
Saadi Bayat
Kok Lian Ho
Noorjahan Banu Mohamed Alitheen
Wen Siang Tan
author_facet Roya Biabanikhankahdani
Saadi Bayat
Kok Lian Ho
Noorjahan Banu Mohamed Alitheen
Wen Siang Tan
author_sort Roya Biabanikhankahdani
collection DOAJ
description Abstract pH-responsive virus-like nanoparticles (VLNPs) hold promising potential as drug delivery systems for cancer therapy. In the present study, hepatitis B virus (HBV) VLNPs harbouring His-tags were used to display doxorubicin (DOX) via nitrilotriacetic acid (NTA) conjugation. The His-tags served as pH-responsive nanojoints which released DOX from VLNPs in a controlled manner. The His-tagged VLNPs conjugated non-covalently with NTA-DOX, and cross-linked with folic acid (FA) were able to specifically target and deliver the DOX into ovarian cancer cells via folate receptor (FR)-mediated endocytosis. The cytotoxicity and cellular uptake results revealed that the His-tagged VLNPs significantly increased the accumulation of DOX in the ovarian cancer cells and enhanced the uptake of DOX, which improved anti-tumour effects. This study demonstrated that NTA-DOX can be easily displayed on His-tagged VLNPs by a simple Add-and-Display step with high coupling efficiency and the drug was only released at low pH in a controlled manner. This approach facilitates specific attachment of any drug molecule on His-tagged VLNPs at the very mild conditions without changing the biological structure and native conformation of the VLNPs.
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spelling doaj.art-2c5f5b747c0243c98b7e3fdad3e3d6442022-12-21T19:08:33ZengNature PortfolioScientific Reports2045-23222017-07-017111210.1038/s41598-017-05525-4A Simple Add-and-Display Method for Immobilisation of Cancer Drug on His-tagged Virus-like Nanoparticles for Controlled Drug DeliveryRoya Biabanikhankahdani0Saadi Bayat1Kok Lian Ho2Noorjahan Banu Mohamed Alitheen3Wen Siang Tan4Department of Microbiology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra MalaysiaDepartment of Chemistry, Faculty of Science, Universiti Putra MalaysiaDepartment of Pathology, Faculty of Medicine and Health Sciences, Universiti Putra MalaysiaDepartment of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra MalaysiaDepartment of Microbiology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra MalaysiaAbstract pH-responsive virus-like nanoparticles (VLNPs) hold promising potential as drug delivery systems for cancer therapy. In the present study, hepatitis B virus (HBV) VLNPs harbouring His-tags were used to display doxorubicin (DOX) via nitrilotriacetic acid (NTA) conjugation. The His-tags served as pH-responsive nanojoints which released DOX from VLNPs in a controlled manner. The His-tagged VLNPs conjugated non-covalently with NTA-DOX, and cross-linked with folic acid (FA) were able to specifically target and deliver the DOX into ovarian cancer cells via folate receptor (FR)-mediated endocytosis. The cytotoxicity and cellular uptake results revealed that the His-tagged VLNPs significantly increased the accumulation of DOX in the ovarian cancer cells and enhanced the uptake of DOX, which improved anti-tumour effects. This study demonstrated that NTA-DOX can be easily displayed on His-tagged VLNPs by a simple Add-and-Display step with high coupling efficiency and the drug was only released at low pH in a controlled manner. This approach facilitates specific attachment of any drug molecule on His-tagged VLNPs at the very mild conditions without changing the biological structure and native conformation of the VLNPs.https://doi.org/10.1038/s41598-017-05525-4
spellingShingle Roya Biabanikhankahdani
Saadi Bayat
Kok Lian Ho
Noorjahan Banu Mohamed Alitheen
Wen Siang Tan
A Simple Add-and-Display Method for Immobilisation of Cancer Drug on His-tagged Virus-like Nanoparticles for Controlled Drug Delivery
Scientific Reports
title A Simple Add-and-Display Method for Immobilisation of Cancer Drug on His-tagged Virus-like Nanoparticles for Controlled Drug Delivery
title_full A Simple Add-and-Display Method for Immobilisation of Cancer Drug on His-tagged Virus-like Nanoparticles for Controlled Drug Delivery
title_fullStr A Simple Add-and-Display Method for Immobilisation of Cancer Drug on His-tagged Virus-like Nanoparticles for Controlled Drug Delivery
title_full_unstemmed A Simple Add-and-Display Method for Immobilisation of Cancer Drug on His-tagged Virus-like Nanoparticles for Controlled Drug Delivery
title_short A Simple Add-and-Display Method for Immobilisation of Cancer Drug on His-tagged Virus-like Nanoparticles for Controlled Drug Delivery
title_sort simple add and display method for immobilisation of cancer drug on his tagged virus like nanoparticles for controlled drug delivery
url https://doi.org/10.1038/s41598-017-05525-4
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