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

Autor: Elizabeth S. Childress, Webster L. Santos, Frank Gillam, Jeannine S. Strobl, Masoud Agah, Chenming Zhang, Vaishnavi Srinivasaraghavan, Hesam Babahosseini, Zongmin Zhao
Rok vydání: 2016
Předmět:
Cell
Biomedical Engineering
Sphingosine kinase
Antineoplastic Agents
Breast Neoplasms
Bioengineering
02 engineering and technology
Electric Capacitance
01 natural sciences
Biochemistry
Structure-Activity Relationship
chemistry.chemical_compound
Drug Delivery Systems
Polylactic Acid-Polyglycolic Acid Copolymer
Single-cell analysis
Cell Line
Tumor
medicine
Humans
Lactic Acid
Protein Kinase Inhibitors
Cell Proliferation
Membrane potential
Molecular Structure
Cell growth
Chemistry
010401 analytical chemistry
technology
industry
and agriculture
General Chemistry
Microfluidic Analytical Techniques
021001 nanoscience & nanotechnology
Biomechanical Phenomena
0104 chemical sciences
3. Good health
Phosphotransferases (Alcohol Group Acceptor)
PLGA
medicine.anatomical_structure
Cancer cell
Drug delivery
Disease Progression
Biophysics
Nanoparticles
Female
Single-Cell Analysis
0210 nano-technology
Polyglycolic Acid
Biomedical engineering
Zdroj: Lab on a Chip
ISSN: 1473-0189
1473-0197
DOI: 10.1039/c5lc01201e
Popis: A microfluidic chip developed to study the effects of free-drug versus NPs-mediated drug delivery on cancer cells using their electromechanical biomarkers.
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.
Databáze: OpenAIRE
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