The impact of sphingosine kinase inhibitor-loaded nanoparticles on bioelectrical and biomechanical properties of cancer cells

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dc.contributor.authorBabahosseini, Hesamen
dc.contributor.authorSrinivasaraghavan, Vaishnavien
dc.contributor.authorZhao, Zongminen
dc.contributor.authorGillam, Francisen
dc.contributor.authorChildress, Elizabethen
dc.contributor.authorStrobl, Jeannine S.en
dc.contributor.authorSantos, Webster L.en
dc.contributor.authorZhang, Chenmingen
dc.contributor.authorAgah, Masouden
dc.contributor.departmentMechanical Engineeringen
dc.contributor.departmentElectrical and Computer Engineeringen
dc.contributor.departmentBiological Systems Engineeringen
dc.contributor.departmentChemistryen
dc.date.accessed2016-03-17en
dc.date.accessioned2016-03-18T22:24:51Zen
dc.date.available2016-03-18T22:24:51Zen
dc.date.issued2015-11-19en
dc.description.abstractCancer progression and physiological changes within the cells are accompanied by alterations in the biophysical properties. Therefore, the cell biophysical properties can serve as promising markers for cancer detection and physiological activities. To aid in the investigation of the biophysical markers of cells, a microfluidic chip has been developed which consists of a constriction channel and embedded microelectrodes. Single-cell impedance magnitudes at four frequencies and entry and travel times are measured simultaneously during their transit through the constriction channel. This microchip provides a high-throughput, label-free, automated assay to identify biophysical signatures of malignant cells and monitor the therapeutic efficacy of drugs. Here, we monitored the dynamic cellular biophysical properties in response to sphingosine kinase inhibitors (SphKIs), and compared the effectiveness of drug delivery using poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) loaded with SphKIs versus conventional delivery. Cells treated with SphKIs showed significantly higher impedance magnitudes at all four frequencies. The bioelectrical parameters extracted using a model also revealed that the highly aggressive breast cells treated with SphKIs shifted electrically towards that of a less malignant phenotype; SphKI-treated cells exhibited an increase in cell-channel interface resistance and a significant decrease in specific membrane capacitance. Furthermore, SphKI-treated cells became slightly more deformable as measured by a decrease in their channel entry and travel times. We observed no significant difference in the bioelectrical changes produced by SphKI delivered conventionally or with NPs. However, NPs-packaged delivery of SphKI decreased the cell deformability. In summary, this study showed that while the bioelectrical properties of the cells were dominantly affected by SphKIs, the biomechanical properties were mainly changed by the NPs.en
dc.description.notes2015 Royal Society of Chemistry Open Access Gold Articleen
dc.description.sponsorshipNational Science Foundation (U.S.)en
dc.description.sponsorshipNational Institutes of Health (U.S.)en
dc.format.extent11 p.en
dc.format.mimetypeapplication/pdfen
dc.identifier.citationBabahosseini, H., Srinivasaraghavan, V., Zhao, Z., Gillam, F., Childress, E., Strobl, J. S., Santos, W. L., Zhang, C., & Agah, M. (2016). The impact of sphingosine kinase inhibitor-loaded nanoparticles on bioelectrical and biomechanical properties of cancer cells. Lab on a Chip, 16(1), 188-198. doi:10.1039/C5LC01201Een
dc.identifier.doihttps://doi.org/10.1039/C5LC01201Een
dc.identifier.issn1473-0197en
dc.identifier.issue1en
dc.identifier.other2016_Babahosseini_The_impact_of_sphingosine.pdfen
dc.identifier.otherCBET-1403304en
dc.identifier.otherU01DA036850en
dc.identifier.urihttp://hdl.handle.net/10919/64947en
dc.identifier.volume16en
dc.language.isoenen
dc.publisherThe Royal Society of Chemistryen
dc.rightsCreative Commons Attribution-NonCommercial 3.0 Unporteden
dc.rights.urihttp://creativecommons.org/licenses/by-nc/3.0/en
dc.titleThe impact of sphingosine kinase inhibitor-loaded nanoparticles on bioelectrical and biomechanical properties of cancer cellsen
dc.title.serialLab on a Chipen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
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