Encapsulation of Docetaxel in Calcium Phosphosilicate Nanoparticles and the Effects of Bioconjugation

Open Access
Author:
Hughes, Kelly E
Area of Honors:
Bioengineering
Degree:
Bachelor of Science
Document Type:
Thesis
Thesis Supervisors:
  • Cheng Dong, Thesis Supervisor
  • James Hansell Adair, Thesis Supervisor
  • William O Hancock, Honors Advisor
Keywords:
  • nanoparticles
  • breast cancer
  • cancer
  • calcium phosphate
Abstract:
Breast cancer is one of the most common and one of the deadliest cancers diagnosed among women. The disease kills nearly 40,000 women each year. Current treatments include surgery and radiation as well as systemic therapies such as hormonal therapy, targeted therapy, and chemotherapy. However, the problem with these systemic therapies is that they are not specific and kill normal body cells in addition to cancer cells causing harmful side effects. Calcium Phosphosilicate nanoparticles (CPSNPs) have the potential to encapsulate chemotherapeutic drugs until they reach the cancerous cells protecting the body from toxic side effects. Previous flow studies were completed using these particles; however, changes in environmental pH proved to cause significant differences in the association of particles with the tumor cells. The current study used MDA-MB-231 breast cancer cells to test the CPSNPs in a pH controlled environment. First, Rhodamine-WT encapsulating citrate, PEG, and anti-CD71 functionalized particles were tested in static, low shear (62.5 sec-1), and high shear (200 sec-1) environments. Fluorescence intensity which corresponds to particle-cell associations was assessed using flow cytometry. Then, docetaxel encapsulating citrate particles were tested using flow migration studies to determine the effect the drugged particles had on extravasation of circulating tumor cells. Results revealed that anti-CD71 functionalized particles experienced significantly increased particle-cell associations compared to citrate particles. Additionally, particle-cell associations were increased under low shear conditions. Flow migration results further support this conclusion and revealed that docetaxel encapsulating citrate particles decrease tumor cell extravasation. Future studies will include additional flow migration studies with citrate functionalized drugged particles as well as studies using PEG and anti-CD71 drugged particles and additional particle cell association studies at shorter and longer time intervals.