title: The impact of sphingosine kinase inhibitor-loaded nanoparticles on bioelectrical and biomechanical properties of cancer cells.
abstract: Cancer 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.
authors.affiliation: Department of Mechanical Engineering, Virginia Tech, Blacksburg, VA 24061, USA.
authors.forename: Hesam
authors.initials: H
authors.lastname: Babahosseini
authors.forename: Vaishnavi
authors.initials: V
authors.lastname: Srinivasaraghavan
authors.forename: Zongmin
authors.initials: Z
authors.lastname: Zhao
authors.forename: Frank
authors.initials: F
authors.lastname: Gillam
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Childress
authors.forename: Jeannine S
authors.initials: JS
authors.lastname: Strobl
authors.forename: Webster L
authors.initials: WL
authors.lastname: Santos
authors.forename: Chenming
authors.initials: C
authors.lastname: Zhang
authors.forename: Masoud
authors.initials: M
authors.lastname: Agah
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D001696:Biomechanical Phenomena / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018450:Disease Progression; D016503:Drug Delivery Systems; D025802:Electric Capacitance; D005260:Female; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation; D015394:Molecular Structure; D053758:Nanoparticles / Q000737:chemistry*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D059010:Single-Cell Analysis / Q000379:methods*; D013329:Structure-Activity Relationship; D000099157:Sphingosine Kinase
chemical_list: D000970:Antineoplastic Agents; D019344:Lactic Acid; D017853:Phosphotransferases (Alcohol Group Acceptor); D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D047428:Protein Kinase Inhibitors; D000099157:Sphingosine Kinase