The effect of bioconjugation of calcium phosphosilicate nanoparticles on breast cancer cell association under shear conditions
Open Access
- Author:
- Harter, Lauren Michele
- Area of Honors:
- Bioengineering
- Degree:
- Bachelor of Science
- Document Type:
- Thesis
- Thesis Supervisors:
- Cheng Dong, Thesis Supervisor
Peter J Butler, Thesis Honors Advisor - Keywords:
- nanoparticles
breast cancer
shear conditions - Abstract:
- Breast cancer is the second leading cause of cancer-related death in American women1. Current chemotherapeutic treatments, while often effective, cause myriad side effects that can lead to serious complications or inability to continue treatment. Calcium phosphosilicate nanoparticles (CPSNPs) are a novel method of chemotherapeutic delivery that release smaller amounts of drug directly into the cancer cell, minimizing the drug’s toxic effects on other parts of the body. These particles also allow for a wide array of surface conjugations, including the addition of antibodies specific to a certain cancer type2,3. In this study, CD71 was targeted due to its prevalence on breast cancer cells. In previous studies, the particle binding and subsequent uptake of these nanoparticles was studied under static conditions. While successful, this approach does not account for the physiological, dynamic flow conditions encountered in vivo. This study seeks to use flow conditions to study the effect of anti-CD71 bioconjugation of CPSNPs in cell-particle association (binding and/or uptake). In this study, anti-CD71 conjugated particles and citrate-functionalized particles were tested using encapsulated rhodamine WT in order to quantify particle-cell association using flow cytometry. The first step in this process was to ensure successful conjugation of the particles. Next the particles were tested under static conditions to determine a baseline from which to measure the shear results. Finally, the particles were tested under both a low (62.5 sec-1) and high (200 sec-1) shear rate, induced by a cone plate viscometer. Both the static and shear experiments required multiple experiments and improvements in order to design an appropriate protocol. The results revealed a significantly higher association of anti-CD71 functionalized CPSNPs with breast cancer cells under both static and low shear conditions, but no significance was found between particle types at high shear. It was also found that these particles are most likely associated by encapsulation within the cell, rather than simply bound to the outside of the cell. However, the location of particles requires further study, as does the therapeutic benefit of increased association and the specificity this benefit has for breast cancer cells.