Skin-derived mesenchymal stem cells as quantum dot vehicles to tumors

Dominyka Dapkute,1,2 Simona Steponkiene,1 Danute Bulotiene,1 Liga Saulite,3 Una Riekstina,3 Ricardas Rotomskis1,4 1Biomedical Physics Laboratory, National Cancer Institute, Vilnius, Lithuania; 2Institute of Biosciences, Vilnius University, Vilnius, Lithuania; 3Faculty of Medicine, University of Lat...

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Autores principales: Dapkute D, Steponkiene S, Bulotiene D, Saulite L, Riekstina U, Rotomskis R
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Publicado: Dove Medical Press 2017
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spelling oai:doaj.org-article:26b796d7c0b146da86b75797317b50092021-12-02T04:28:18ZSkin-derived mesenchymal stem cells as quantum dot vehicles to tumors1178-2013https://doaj.org/article/26b796d7c0b146da86b75797317b50092017-11-01T00:00:00Zhttps://www.dovepress.com/skin-derived-mesenchymal-stem-cells-as-quantum-dot-vehicles-to-tumors-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Dominyka Dapkute,1,2 Simona Steponkiene,1 Danute Bulotiene,1 Liga Saulite,3 Una Riekstina,3 Ricardas Rotomskis1,4 1Biomedical Physics Laboratory, National Cancer Institute, Vilnius, Lithuania; 2Institute of Biosciences, Vilnius University, Vilnius, Lithuania; 3Faculty of Medicine, University of Latvia, Riga, Latvia; 4Biophotonics Group of Laser Research Center, Faculty of Physics, Vilnius University, Vilnius, Lithuania Purpose: Cell-mediated delivery of nanoparticles is emerging as a new method of cancer diagnostics and treatment. Due to their inherent regenerative properties, adult mesenchymal stem cells (MSCs) are naturally attracted to wounds and sites of inflammation, as well as tumors. Such characteristics enable MSCs to be used in cellular hitchhiking of nanoparticles. In this study, MSCs extracted from the skin connective tissue were investigated as transporters of semiconductor nanocrystals quantum dots (QDs).Materials and methods: Cytotoxicity of carboxylated CdSe/ZnS QDs was assessed by lactate dehydrogenase cell viability assay. Quantitative uptake of QDs was determined by flow cytometry; their intracellular localization was evaluated by confocal microscopy. In vitro tumor-tropic migration of skin-derived MSCs was verified by Transwell migration assay. For in vivo migration studies of QD-loaded MSCs, human breast tumor-bearing immunodeficient mice were used.Results: QDs were found to be nontoxic to MSCs in concentrations no more than 16 nM. The uptake studies showed a rapid QD endocytosis followed by saturating effects after 6 h of incubation and intracellular localization in the perinuclear region. In vitro migration of MSCs toward MDA-MB-231 breast cancer cells and their conditioned medium was up to nine times greater than the migration toward noncancerous breast epithelial cells MCF-10A. In vivo, systemically administered QD-labeled MSCs were mainly located in the tumor and metastatic tissues, evading most healthy organs with the exception being blood clearance organs (spleen, kidneys, liver).Conclusion: Skin-derived MSCs demonstrate applicability in cell-mediated delivery of nanoparticles. The findings presented in this study promise further development of a cell therapy and nanotechnology-based tool for early cancer diagnostics and therapy. Keywords: mesenchymal stem cells, tumor tropism, quantum dots, nanoparticles, tumor-specific delivery, immunodeficient miceDapkute DSteponkiene SBulotiene DSaulite LRiekstina URotomskis RDove Medical PressarticleMesenchymal stem cells (MSCs)tumor tropismquantum dots (QDs)nanoparticlestumor-specific deliveryMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 8129-8142 (2017)
institution DOAJ
collection DOAJ
language EN
topic Mesenchymal stem cells (MSCs)
tumor tropism
quantum dots (QDs)
nanoparticles
tumor-specific delivery
Medicine (General)
R5-920
spellingShingle Mesenchymal stem cells (MSCs)
tumor tropism
quantum dots (QDs)
nanoparticles
tumor-specific delivery
Medicine (General)
R5-920
Dapkute D
Steponkiene S
Bulotiene D
Saulite L
Riekstina U
Rotomskis R
Skin-derived mesenchymal stem cells as quantum dot vehicles to tumors
description Dominyka Dapkute,1,2 Simona Steponkiene,1 Danute Bulotiene,1 Liga Saulite,3 Una Riekstina,3 Ricardas Rotomskis1,4 1Biomedical Physics Laboratory, National Cancer Institute, Vilnius, Lithuania; 2Institute of Biosciences, Vilnius University, Vilnius, Lithuania; 3Faculty of Medicine, University of Latvia, Riga, Latvia; 4Biophotonics Group of Laser Research Center, Faculty of Physics, Vilnius University, Vilnius, Lithuania Purpose: Cell-mediated delivery of nanoparticles is emerging as a new method of cancer diagnostics and treatment. Due to their inherent regenerative properties, adult mesenchymal stem cells (MSCs) are naturally attracted to wounds and sites of inflammation, as well as tumors. Such characteristics enable MSCs to be used in cellular hitchhiking of nanoparticles. In this study, MSCs extracted from the skin connective tissue were investigated as transporters of semiconductor nanocrystals quantum dots (QDs).Materials and methods: Cytotoxicity of carboxylated CdSe/ZnS QDs was assessed by lactate dehydrogenase cell viability assay. Quantitative uptake of QDs was determined by flow cytometry; their intracellular localization was evaluated by confocal microscopy. In vitro tumor-tropic migration of skin-derived MSCs was verified by Transwell migration assay. For in vivo migration studies of QD-loaded MSCs, human breast tumor-bearing immunodeficient mice were used.Results: QDs were found to be nontoxic to MSCs in concentrations no more than 16 nM. The uptake studies showed a rapid QD endocytosis followed by saturating effects after 6 h of incubation and intracellular localization in the perinuclear region. In vitro migration of MSCs toward MDA-MB-231 breast cancer cells and their conditioned medium was up to nine times greater than the migration toward noncancerous breast epithelial cells MCF-10A. In vivo, systemically administered QD-labeled MSCs were mainly located in the tumor and metastatic tissues, evading most healthy organs with the exception being blood clearance organs (spleen, kidneys, liver).Conclusion: Skin-derived MSCs demonstrate applicability in cell-mediated delivery of nanoparticles. The findings presented in this study promise further development of a cell therapy and nanotechnology-based tool for early cancer diagnostics and therapy. Keywords: mesenchymal stem cells, tumor tropism, quantum dots, nanoparticles, tumor-specific delivery, immunodeficient mice
format article
author Dapkute D
Steponkiene S
Bulotiene D
Saulite L
Riekstina U
Rotomskis R
author_facet Dapkute D
Steponkiene S
Bulotiene D
Saulite L
Riekstina U
Rotomskis R
author_sort Dapkute D
title Skin-derived mesenchymal stem cells as quantum dot vehicles to tumors
title_short Skin-derived mesenchymal stem cells as quantum dot vehicles to tumors
title_full Skin-derived mesenchymal stem cells as quantum dot vehicles to tumors
title_fullStr Skin-derived mesenchymal stem cells as quantum dot vehicles to tumors
title_full_unstemmed Skin-derived mesenchymal stem cells as quantum dot vehicles to tumors
title_sort skin-derived mesenchymal stem cells as quantum dot vehicles to tumors
publisher Dove Medical Press
publishDate 2017
url https://doaj.org/article/26b796d7c0b146da86b75797317b5009
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AT saulitel skinderivedmesenchymalstemcellsasquantumdotvehiclestotumors
AT riekstinau skinderivedmesenchymalstemcellsasquantumdotvehiclestotumors
AT rotomskisr skinderivedmesenchymalstemcellsasquantumdotvehiclestotumors
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