Cellular trafficking and anticancer activity of Garcinia mangostana extract-encapsulated polymeric nanoparticles

Porntip Pan-In,1,2 Supason Wanichwecharungruang,3,4 Justin Hanes,2,5 Anthony J Kim2,6,7 1Program in Biotechnology, Faculty of Science, Chulalongkorn University, Bangkok, Thailand; 2Center for Nanomedicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA; 3Department of Chemistry, F...

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Autores principales: Pan-In P, Wanichwecharungruang S, Hanes J, Kim AJ
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Publicado: Dove Medical Press 2014
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spelling oai:doaj.org-article:da8f1e5335b84721922594bba444eb132021-12-02T01:50:38ZCellular trafficking and anticancer activity of Garcinia mangostana extract-encapsulated polymeric nanoparticles1178-2013https://doaj.org/article/da8f1e5335b84721922594bba444eb132014-08-01T00:00:00Zhttp://www.dovepress.com/cellular-trafficking-and-anticancer-activity-of-garcinia-mangostana-ex-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013 Porntip Pan-In,1,2 Supason Wanichwecharungruang,3,4 Justin Hanes,2,5 Anthony J Kim2,6,7 1Program in Biotechnology, Faculty of Science, Chulalongkorn University, Bangkok, Thailand; 2Center for Nanomedicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA; 3Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok, Thailand; 4Nanotec-CU Center of Excellence on Food and Agriculture, Bangkok, Thailand; 5Department of Ophthalmology, Biomedical Engineering, Chemical and Biomolecular Engineering, Neurosurgery, and Oncology, Johns Hopkins University School of Medicine, 6Department of Neurosurgery, University of Maryland School of Medicine, 7Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD, USA Abstract: Garcinia mangostana Linn extract (GME) is a natural product that has received considerable attention in cancer therapy, and has the potential to reduce side effects of chemotherapeutics and improve efficacy. We formulated GME-encapsulated ethyl cellulose (GME-EC) and a polymer blend of ethyl cellulose and methyl cellulose (GME-EC/MC) nanoparticles. We achieved high drug-loading and encapsulation efficiency using a solvent-displacement method with particle sizes around 250 nm. Cellular uptake and accumulation of GME was higher for GME-encapsulated nanoparticles compared to free GME. In vitro cytotoxicity analysis showed effective anticancer activity of GME-EC and GME-EC/MC nanoparticles in HeLa cells in a dose-dependent manner. GME-EC/MC nanoparticles showed approximately twofold-higher anticancer activity compared to GME-EC nanoparticles, likely due to their enhanced bioavailability. GME-encapsulated nanoparticles primarily entered HeLa cells by clathrin-mediated endocytosis and trafficked through the endolysosomal pathway. As far as we know, this is the first report on the cellular uptake and intracellular trafficking mechanism of drug-loaded cellulose-based nanoparticles. In summary, encapsulation of GME using cellulose-derivative nanoparticles – GME-EC and GME-EC/MC nanoparticles – successfully improved the bioavailability of GME in aqueous solution, enhanced cellular uptake, and displayed effective anticancer activity. Keywords: phytotherapy, cancer, nanoparticles, cellulose, intracellular traffickingPan-In PWanichwecharungruang SHanes JKim AJDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2014, Iss Issue 1, Pp 3677-3686 (2014)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Pan-In P
Wanichwecharungruang S
Hanes J
Kim AJ
Cellular trafficking and anticancer activity of Garcinia mangostana extract-encapsulated polymeric nanoparticles
description Porntip Pan-In,1,2 Supason Wanichwecharungruang,3,4 Justin Hanes,2,5 Anthony J Kim2,6,7 1Program in Biotechnology, Faculty of Science, Chulalongkorn University, Bangkok, Thailand; 2Center for Nanomedicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA; 3Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok, Thailand; 4Nanotec-CU Center of Excellence on Food and Agriculture, Bangkok, Thailand; 5Department of Ophthalmology, Biomedical Engineering, Chemical and Biomolecular Engineering, Neurosurgery, and Oncology, Johns Hopkins University School of Medicine, 6Department of Neurosurgery, University of Maryland School of Medicine, 7Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD, USA Abstract: Garcinia mangostana Linn extract (GME) is a natural product that has received considerable attention in cancer therapy, and has the potential to reduce side effects of chemotherapeutics and improve efficacy. We formulated GME-encapsulated ethyl cellulose (GME-EC) and a polymer blend of ethyl cellulose and methyl cellulose (GME-EC/MC) nanoparticles. We achieved high drug-loading and encapsulation efficiency using a solvent-displacement method with particle sizes around 250 nm. Cellular uptake and accumulation of GME was higher for GME-encapsulated nanoparticles compared to free GME. In vitro cytotoxicity analysis showed effective anticancer activity of GME-EC and GME-EC/MC nanoparticles in HeLa cells in a dose-dependent manner. GME-EC/MC nanoparticles showed approximately twofold-higher anticancer activity compared to GME-EC nanoparticles, likely due to their enhanced bioavailability. GME-encapsulated nanoparticles primarily entered HeLa cells by clathrin-mediated endocytosis and trafficked through the endolysosomal pathway. As far as we know, this is the first report on the cellular uptake and intracellular trafficking mechanism of drug-loaded cellulose-based nanoparticles. In summary, encapsulation of GME using cellulose-derivative nanoparticles – GME-EC and GME-EC/MC nanoparticles – successfully improved the bioavailability of GME in aqueous solution, enhanced cellular uptake, and displayed effective anticancer activity. Keywords: phytotherapy, cancer, nanoparticles, cellulose, intracellular trafficking
format article
author Pan-In P
Wanichwecharungruang S
Hanes J
Kim AJ
author_facet Pan-In P
Wanichwecharungruang S
Hanes J
Kim AJ
author_sort Pan-In P
title Cellular trafficking and anticancer activity of Garcinia mangostana extract-encapsulated polymeric nanoparticles
title_short Cellular trafficking and anticancer activity of Garcinia mangostana extract-encapsulated polymeric nanoparticles
title_full Cellular trafficking and anticancer activity of Garcinia mangostana extract-encapsulated polymeric nanoparticles
title_fullStr Cellular trafficking and anticancer activity of Garcinia mangostana extract-encapsulated polymeric nanoparticles
title_full_unstemmed Cellular trafficking and anticancer activity of Garcinia mangostana extract-encapsulated polymeric nanoparticles
title_sort cellular trafficking and anticancer activity of garcinia mangostana extract-encapsulated polymeric nanoparticles
publisher Dove Medical Press
publishDate 2014
url https://doaj.org/article/da8f1e5335b84721922594bba444eb13
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AT wanichwecharungruangs cellulartraffickingandanticanceractivityofgarciniamangostanaextractencapsulatedpolymericnanoparticles
AT hanesj cellulartraffickingandanticanceractivityofgarciniamangostanaextractencapsulatedpolymericnanoparticles
AT kimaj cellulartraffickingandanticanceractivityofgarciniamangostanaextractencapsulatedpolymericnanoparticles
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