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: Wenliang Fu, Mohd Hezmee Mohd Noor, Loqman Mohamad Yusof, Tengku Azmi Tengku Ibrahim, Yeap Swee Keong, Alhaji Zubair Jaji, Md Zuki Abu Bakar Zakaria
Format: Article
Language:English
Published: Taylor & Francis Group 2017-01-01
Series:Journal of Experimental Nanoscience
Subjects:
Online Access:http://dx.doi.org/10.1080/17458080.2017.1287965
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author Wenliang Fu
Mohd Hezmee Mohd Noor
Loqman Mohamad Yusof
Tengku Azmi Tengku Ibrahim
Yeap Swee Keong
Alhaji Zubair Jaji
Md Zuki Abu Bakar Zakaria
author_facet Wenliang Fu
Mohd Hezmee Mohd Noor
Loqman Mohamad Yusof
Tengku Azmi Tengku Ibrahim
Yeap Swee Keong
Alhaji Zubair Jaji
Md Zuki Abu Bakar Zakaria
author_sort Wenliang Fu
collection DOAJ
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 doaj.art-3c7f69d1e5954c31878b4a8a0935a7352022-12-21T17:51:05ZengTaylor & Francis GroupJournal of Experimental Nanoscience1745-80801745-80992017-01-0112116618710.1080/17458080.2017.12879651287965In vitro evaluation of a novel pH sensitive drug delivery system based cockle shell-derived aragonite nanoparticles against osteosarcomaWenliang Fu0Mohd Hezmee Mohd Noor1Loqman Mohamad Yusof2Tengku Azmi Tengku Ibrahim3Yeap Swee Keong4Alhaji Zubair Jaji5Md Zuki Abu Bakar Zakaria6Universiti Putra MalaysiaUniversiti Putra MalaysiaUniversiti Putra MalaysiaUniversiti Putra MalaysiaUniversiti Putra MalaysiaChengde Medical UniversityChengde Medical UniversityBackground: 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.http://dx.doi.org/10.1080/17458080.2017.1287965cockle shellaragonitenanoparticlespH-sensitivedrug deliverydoxorubicinosteosarcoma
spellingShingle Wenliang Fu
Mohd Hezmee Mohd Noor
Loqman Mohamad Yusof
Tengku Azmi Tengku Ibrahim
Yeap Swee Keong
Alhaji Zubair Jaji
Md Zuki Abu Bakar Zakaria
In vitro evaluation of a novel pH sensitive drug delivery system based cockle shell-derived aragonite nanoparticles against osteosarcoma
Journal of Experimental Nanoscience
cockle shell
aragonite
nanoparticles
pH-sensitive
drug delivery
doxorubicin
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
topic cockle shell
aragonite
nanoparticles
pH-sensitive
drug delivery
doxorubicin
osteosarcoma
url http://dx.doi.org/10.1080/17458080.2017.1287965
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