In vitro evaluation of a novel pH sensitive drug delivery system based cockle shell-derived aragonite nanoparticles against osteosarcoma

Background: Osteosarcoma (OS) is a highly malignant primary bone cancer. Severe side effects and multidrug resistance are obstacles faced with chemotherapy against OS. With the hope to overcome the obstacles of the conventional chemotherapy, various targeted drug delivery systems using nanotechnolog...

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Main Authors: Fu, Wenliang, Mohd Noor, Mohd Hezmee, Mohamad Yusof, Loqman, Tengku Ibrahim, Tengku Azmi, Keong, Yeap Swee, Jaji, Alhaji Zubair, Abu Bakar @ Zakaria, Md Zuki
Format: Article
Language:English
Published: Taylor & Francis 2017
Online Access:http://psasir.upm.edu.my/id/eprint/62138/
http://psasir.upm.edu.my/id/eprint/62138/1/In%20vitro%20evaluation%20of%20a%20novel%20pH%20sensitive%20drug%20delivery%20system%20based%20cockle%20shell-derived%20aragonite%20nanoparticles%20against%20osteosarcoma.pdf
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author Fu, Wenliang
Mohd Noor, Mohd Hezmee
Mohamad Yusof, Loqman
Tengku Ibrahim, Tengku Azmi
Keong, Yeap Swee
Jaji, Alhaji Zubair
Abu Bakar @ Zakaria, Md Zuki
author_facet Fu, Wenliang
Mohd Noor, Mohd Hezmee
Mohamad Yusof, Loqman
Tengku Ibrahim, Tengku Azmi
Keong, Yeap Swee
Jaji, Alhaji Zubair
Abu Bakar @ Zakaria, Md Zuki
author_sort Fu, Wenliang
building UPM Institutional Repository
collection Online Access
description Background: Osteosarcoma (OS) is a highly malignant primary bone cancer. Severe side effects and multidrug resistance are obstacles faced with chemotherapy against OS. With the hope to overcome the obstacles of the conventional chemotherapy, various targeted drug delivery systems using nanotechnology have been explored in the past few decades. Biogenic calcium carbonate (CaCO3) has great potential to be a smart drug delivery system. Results: In this study, cockle shells-derived aragonite nanoparticles (ANPs) were developed and loaded with doxorubicin (DOX). The physicochemical properties of the DOX-loaded ANPs (DOX-ANPs) were characterised by various techniques. The results of drug-loading study demonstrated that DOX was loaded onto ANPs at high loading and encapsulation efficiency (11.09% and 99.58%, respectively). The pH-sensitive release of DOX from DOX-ANPs was successful. At lower pH values (4.8), the release of DOX was much quicker than that at pH 7.4. Additionally, cellular uptake study using fluorescence microscopy showed obviously cellular uptake of DOX-ANPs through endocytosis. Moreover, the flow cytometric analysis revealed DOX-ANPs-induced cell cycle arrest, which was consistent with the mechanism of DOX. DOX-ANPs also showed an efficient cytotoxicity against OS cancer cells, close to the toxicity effect of free DOX at the same concentration. Morphological observations showed microvilli disappearance, chromatin condensation, cell shrinkage, membrane blebbing, and formation of apoptotic bodies, which confirmed both DOX-ANPs- and DOX-induced apoptosis of OS cancer cells in vitro. Conclusion: Our findings indicated that ANPs could act as a pH-sensitive drug delivery against OS.
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spelling upm-621382019-04-16T03:02:27Z http://psasir.upm.edu.my/id/eprint/62138/ In vitro evaluation of a novel pH sensitive drug delivery system based cockle shell-derived aragonite nanoparticles against osteosarcoma Fu, Wenliang Mohd Noor, Mohd Hezmee Mohamad Yusof, Loqman Tengku Ibrahim, Tengku Azmi Keong, Yeap Swee Jaji, Alhaji Zubair Abu Bakar @ Zakaria, Md Zuki Background: Osteosarcoma (OS) is a highly malignant primary bone cancer. Severe side effects and multidrug resistance are obstacles faced with chemotherapy against OS. With the hope to overcome the obstacles of the conventional chemotherapy, various targeted drug delivery systems using nanotechnology have been explored in the past few decades. Biogenic calcium carbonate (CaCO3) has great potential to be a smart drug delivery system. Results: In this study, cockle shells-derived aragonite nanoparticles (ANPs) were developed and loaded with doxorubicin (DOX). The physicochemical properties of the DOX-loaded ANPs (DOX-ANPs) were characterised by various techniques. The results of drug-loading study demonstrated that DOX was loaded onto ANPs at high loading and encapsulation efficiency (11.09% and 99.58%, respectively). The pH-sensitive release of DOX from DOX-ANPs was successful. At lower pH values (4.8), the release of DOX was much quicker than that at pH 7.4. Additionally, cellular uptake study using fluorescence microscopy showed obviously cellular uptake of DOX-ANPs through endocytosis. Moreover, the flow cytometric analysis revealed DOX-ANPs-induced cell cycle arrest, which was consistent with the mechanism of DOX. DOX-ANPs also showed an efficient cytotoxicity against OS cancer cells, close to the toxicity effect of free DOX at the same concentration. Morphological observations showed microvilli disappearance, chromatin condensation, cell shrinkage, membrane blebbing, and formation of apoptotic bodies, which confirmed both DOX-ANPs- and DOX-induced apoptosis of OS cancer cells in vitro. Conclusion: Our findings indicated that ANPs could act as a pH-sensitive drug delivery against OS. Taylor & Francis 2017 Article PeerReviewed text en http://psasir.upm.edu.my/id/eprint/62138/1/In%20vitro%20evaluation%20of%20a%20novel%20pH%20sensitive%20drug%20delivery%20system%20based%20cockle%20shell-derived%20aragonite%20nanoparticles%20against%20osteosarcoma.pdf Fu, Wenliang and Mohd Noor, Mohd Hezmee and Mohamad Yusof, Loqman and Tengku Ibrahim, Tengku Azmi and Keong, Yeap Swee and Jaji, Alhaji Zubair and Abu Bakar @ Zakaria, Md Zuki (2017) In vitro evaluation of a novel pH sensitive drug delivery system based cockle shell-derived aragonite nanoparticles against osteosarcoma. Journal of Experimental Nanoscience, 12 (1). 166 - 187. ISSN 1745-8080; ESSN: 1745-8099 https://www.tandfonline.com/doi/full/10.1080/17458080.2017.1287965 10.1080/17458080.2017.1287965
spellingShingle Fu, Wenliang
Mohd Noor, Mohd Hezmee
Mohamad Yusof, Loqman
Tengku Ibrahim, Tengku Azmi
Keong, Yeap Swee
Jaji, Alhaji Zubair
Abu Bakar @ Zakaria, Md Zuki
In vitro evaluation of a novel pH sensitive drug delivery system based cockle shell-derived aragonite nanoparticles against osteosarcoma
title In vitro evaluation of a novel pH sensitive drug delivery system based cockle shell-derived aragonite nanoparticles against osteosarcoma
title_full In vitro evaluation of a novel pH sensitive drug delivery system based cockle shell-derived aragonite nanoparticles against osteosarcoma
title_fullStr In vitro evaluation of a novel pH sensitive drug delivery system based cockle shell-derived aragonite nanoparticles against osteosarcoma
title_full_unstemmed In vitro evaluation of a novel pH sensitive drug delivery system based cockle shell-derived aragonite nanoparticles against osteosarcoma
title_short In vitro evaluation of a novel pH sensitive drug delivery system based cockle shell-derived aragonite nanoparticles against osteosarcoma
title_sort in vitro evaluation of a novel ph sensitive drug delivery system based cockle shell-derived aragonite nanoparticles against osteosarcoma
url http://psasir.upm.edu.my/id/eprint/62138/
http://psasir.upm.edu.my/id/eprint/62138/
http://psasir.upm.edu.my/id/eprint/62138/
http://psasir.upm.edu.my/id/eprint/62138/1/In%20vitro%20evaluation%20of%20a%20novel%20pH%20sensitive%20drug%20delivery%20system%20based%20cockle%20shell-derived%20aragonite%20nanoparticles%20against%20osteosarcoma.pdf