Folic acid targeted Mn:ZnS quantum dots for theranostic applications of cancer cell imaging and therapy
In this study, we synthesized a multifunctional nanoparticulate system with specific targeting, imaging, and drug delivering functionalities by following a three-step protocol that operates at room temperature and solely in aqueous media. The synthesis involves the encapsulation of luminescent Mn:Zn...
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2016
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my.upm.eprints.167782016-06-08T03:40:32Z http://psasir.upm.edu.my/id/eprint/16778/ Folic acid targeted Mn:ZnS quantum dots for theranostic applications of cancer cell imaging and therapy Bwatanglang, Ibrahim Birma Mohammad, Faruq Yusof, Nor Azah Abdullah, Jaafar Hussein, Mohd Zobir Mohammed Alitheen, Noorjahan Banu Abu, Nadiah In this study, we synthesized a multifunctional nanoparticulate system with specific targeting, imaging, and drug delivering functionalities by following a three-step protocol that operates at room temperature and solely in aqueous media. The synthesis involves the encapsulation of luminescent Mn:ZnS quantum dots (QDs) with chitosan not only as a stabilizer in biological environment, but also to further provide active binding sites for the conjugation of other biomolecules. Folic acid was incorporated as targeting agent for the specific targeting of the nanocarrier toward the cells overexpressing folate receptors. Thus, the formed composite emits orange–red fluorescence around 600 nm and investigated to the highest intensity at Mn2+ doping concentration of 15 at.% and relatively more stable at low acidic and low alkaline pH levels. The structural characteristics and optical properties were thoroughly analyzed by using Fourier transform infrared, X-ray diffraction, dynamic light scattering, ultraviolet-visible, and fluorescence spectroscopy. Further characterization was conducted using thermogravimetric analysis, high-resolution transmission electron microscopy, field emission scanning electron microscopy, energy dispersive X-ray spectroscopy, X-ray fluorescence, and X-ray photoelectron spectroscopy. The cell viability and proliferation studies by means of MTT assay have demonstrated that the as-synthesized composites do not exhibit any toxicity toward the human breast cell line MCF-10 (noncancer) and the breast cancer cell lines (MCF-7 and MDA-MB-231) up to a 500 µg/mL concentration. The cellular uptake of the nanocomposites was assayed by confocal laser scanning microscope by taking advantage of the conjugated Mn:ZnS QDs as fluorescence makers. The result showed that the functionalization of the chitosan-encapsulated QDs with folic acid enhanced the internalization and binding affinity of the nanocarrier toward folate receptor-overexpressed cells. Therefore, we hypothesized that due to the nontoxic nature of the composite, the as-synthesized nanoparticulate system can be used as a promising candidate for theranostic applications, especially for a simultaneous targeted drug delivery and cellular imaging. Dove Medical Press 2016 Article PeerReviewed application/pdf en http://psasir.upm.edu.my/id/eprint/16778/1/16778.pdf Bwatanglang, Ibrahim Birma and Mohammad, Faruq and Yusof, Nor Azah and Abdullah, Jaafar and Hussein, Mohd Zobir and Mohammed Alitheen, Noorjahan Banu and Abu, Nadiah (2016) Folic acid targeted Mn:ZnS quantum dots for theranostic applications of cancer cell imaging and therapy. International Journal of Nanomedicine, 11. pp. 413-428. ISSN 1176-9114; ESSN: 1178-2013 https://www.dovepress.com/folic-acid-targeted-mnzns-quantum-dots-for-theranostic-applications-of-peer-reviewed-article-IJN 10.2147/IJN.S90198 |
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In this study, we synthesized a multifunctional nanoparticulate system with specific targeting, imaging, and drug delivering functionalities by following a three-step protocol that operates at room temperature and solely in aqueous media. The synthesis involves the encapsulation of luminescent Mn:ZnS quantum dots (QDs) with chitosan not only as a stabilizer in biological environment, but also to further provide active binding sites for the conjugation of other biomolecules. Folic acid was incorporated as targeting agent for the specific targeting of the nanocarrier toward the cells overexpressing folate receptors. Thus, the formed composite emits orange–red fluorescence around 600 nm and investigated to the highest intensity at Mn2+ doping concentration of 15 at.% and relatively more stable at low acidic and low alkaline pH levels. The structural characteristics and optical properties were thoroughly analyzed by using Fourier transform infrared, X-ray diffraction, dynamic light scattering, ultraviolet-visible, and fluorescence spectroscopy. Further characterization was conducted using thermogravimetric analysis, high-resolution transmission electron microscopy, field emission scanning electron microscopy, energy dispersive X-ray spectroscopy, X-ray fluorescence, and X-ray photoelectron spectroscopy. The cell viability and proliferation studies by means of MTT assay have demonstrated that the as-synthesized composites do not exhibit any toxicity toward the human breast cell line MCF-10 (noncancer) and the breast cancer cell lines (MCF-7 and MDA-MB-231) up to a 500 µg/mL concentration. The cellular uptake of the nanocomposites was assayed by confocal laser scanning microscope by taking advantage of the conjugated Mn:ZnS QDs as fluorescence makers. The result showed that the functionalization of the chitosan-encapsulated QDs with folic acid enhanced the internalization and binding affinity of the nanocarrier toward folate receptor-overexpressed cells. Therefore, we hypothesized that due to the nontoxic nature of the composite, the as-synthesized nanoparticulate system can be used as a promising candidate for theranostic applications, especially for a simultaneous targeted drug delivery and cellular imaging. |
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Article |
author |
Bwatanglang, Ibrahim Birma Mohammad, Faruq Yusof, Nor Azah Abdullah, Jaafar Hussein, Mohd Zobir Mohammed Alitheen, Noorjahan Banu Abu, Nadiah |
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Bwatanglang, Ibrahim Birma Mohammad, Faruq Yusof, Nor Azah Abdullah, Jaafar Hussein, Mohd Zobir Mohammed Alitheen, Noorjahan Banu Abu, Nadiah Folic acid targeted Mn:ZnS quantum dots for theranostic applications of cancer cell imaging and therapy |
author_facet |
Bwatanglang, Ibrahim Birma Mohammad, Faruq Yusof, Nor Azah Abdullah, Jaafar Hussein, Mohd Zobir Mohammed Alitheen, Noorjahan Banu Abu, Nadiah |
author_sort |
Bwatanglang, Ibrahim Birma |
title |
Folic acid targeted Mn:ZnS quantum dots for theranostic applications of cancer cell imaging and therapy |
title_short |
Folic acid targeted Mn:ZnS quantum dots for theranostic applications of cancer cell imaging and therapy |
title_full |
Folic acid targeted Mn:ZnS quantum dots for theranostic applications of cancer cell imaging and therapy |
title_fullStr |
Folic acid targeted Mn:ZnS quantum dots for theranostic applications of cancer cell imaging and therapy |
title_full_unstemmed |
Folic acid targeted Mn:ZnS quantum dots for theranostic applications of cancer cell imaging and therapy |
title_sort |
folic acid targeted mn:zns quantum dots for theranostic applications of cancer cell imaging and therapy |
publisher |
Dove Medical Press |
publishDate |
2016 |
url |
http://psasir.upm.edu.my/id/eprint/16778/1/16778.pdf http://psasir.upm.edu.my/id/eprint/16778/ https://www.dovepress.com/folic-acid-targeted-mnzns-quantum-dots-for-theranostic-applications-of-peer-reviewed-article-IJN |
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1643826316220301312 |
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13.214268 |