Nanoparticle-Based Drug Delivery and the Impacts on Cancer Cell Biophysical Markers

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 define biophysical signatures of malignant cells and monitor the therapeutic efficacy of drugs. Here, we monitored the dynamic cellular biophysical markers 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, the results showed that while the bioelectrical properties of the cells were dominantly affected by SphKIs, the biomechanical properties were mainly changed by the NPs.

Name thesis:degree_name

Master of Science

Level thesis:degree_level

masters

Discipline thesis:degree_discipline

Biological Systems Engineering

Department dc:contributor.department

Biological Systems Engineering

Grantor dc:publisher

Virginia Tech

Year dc:date.issued

2015

Author dc:creator

• Babahosseini, Hesam

Chairs dc:contributor.committeechair

• Zhang, Chenming Mike
• Agah, Masoud

Committee member dc:contributor.committeemember

• Santos, Webster L.

• MicroElectroMechanical Systems (MEMS)
• Microfluidics
• Biosensor
• Nanoparticles
• Drug Delivery
• Biomechanics
• Bioelectronics
• Breast Cancer
• MDA-MB-231
• Sphingosine Kinase Inhibitors

Statement dc:rights

• In Copyright

Licence dc:rights.uri

• http://rightsstatements.org/vocab/InC/1.0/

Language dc:language.iso

en_US

Dc Identifier Other

etd-10022015-090213

OAI identifier oai:identifier

oai:vtechworks.lib.vt.edu:10919/79689