Skin-derived mesenchymal stem cells as quantum dot vehicles to tumors
| Autor: | Liga Saulite, Danute Bulotiene, Una Riekstina, Dominyka Dapkute, Ricardas Rotomskis, Simona Steponkiene |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Biophysics Pharmaceutical Science Connective tissue Bioengineering Breast Neoplasms quantum dots Mice SCID Flow cytometry Biomaterials Cell therapy 03 medical and health sciences In vivo Cell Movement International Journal of Nanomedicine Cell Line Tumor Drug Discovery medicine Animals Humans Viability assay Particle Size Cytotoxicity Cell Shape Skin Original Research mesenchymal stem cells Migration Assay medicine.diagnostic_test Cell Death Chemistry Organic Chemistry Mesenchymal stem cell General Medicine Dynamic Light Scattering Endocytosis 030104 developmental biology medicine.anatomical_structure immunodeficient mice Cancer research Nanoparticles Female tumor tropism tumor-specific delivery |
| Zdroj: | International Journal of Nanomedicine |
| ISSN: | 1178-2013 |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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