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A Ternary Drug Delivery Complex to Target CD44 Over Expressing Cancerous Cell Lines
Johnston, Alyssa N.

2012, BS, Kent State University, College of Arts and Sciences / Department of Chemistry.

Targeted drug delivery via nanoparticles is an emerging field that has great potential in the improvement of cancer treatment. The goal of this project is to develop a multi-component drug delivery system that targets and selectively delivers the chemotherapeutic drug, Dox, to cancerous cell lines that over express the cell surface glycoprotein CD44, a receptor for hyaluronic acid. 10nm gold nanoparticles (GNPs) were used as the delivery vehicle for a thiolated derivative of Doxorubicin referred to as MPDOX. In order to target the tumorigenic cell lines that over expressed CD44 receptors, reducing end thiolated hyaluronic acid was used as the targeting ligand. After the individual facets of the nanoconjugate system were synthesized, the optimal conditions for stable nanoconjugate assembly were determined. The stability of the nanoconjugate system was then assessed with a salt stability assay that determined the level of protection hyaluronic acid provided for the nanosystem in the presence of a salt solution. The presence of both the targeting ligand and drug on the resulting nanoconjugates was then demonstrated by UV absorbance to confirm the formation of the full 3-part nanoconjugate system. After the composition of the nanoconjugates was determined, MTS assays were performed in order to generate dose dependent cell viability curves and IC50 values for treatment of two ovarian cancer cell lines (A2008, C-13) with either the free drug or the nanoconjugate system at various time points. The IC50 values were then compared to determine the type of treatment that was most efficient.


When compared to the free drug, equal levels of cytotoxicity were observed in the cancerous cells. However, it was noted that a decrease in cytotoxicity in the non-targeted cells was not observed. It can be concluded that future work is needed to enhance of efficacy of the nanosystem to target cancerous cell lines over non-cancerous cells. Confocal studies were then performed to visualize the uptake of Doxorubicin and MPDOX in cellular compartments. The findings from this project may provide new insights that can be helpful in future cancer tissue specific targeted drug delivery.

Soumitra Basu, PhD (Advisor)
Nicola Brasch, PhD (Committee Member)
Edgar Koojiman, PhD (Committee Member)
Brett Ellman, PhD (Committee Member)
54 p.

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Johnston, A. (2012). A Ternary Drug Delivery Complex to Target CD44 Over Expressing Cancerous Cell Lines. (Electronic Thesis or Dissertation). Retrieved from https://etd.ohiolink.edu/

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Johnston, Alyssa. "A Ternary Drug Delivery Complex to Target CD44 Over Expressing Cancerous Cell Lines." Electronic Thesis or Dissertation. Kent State University, 2012. OhioLINK Electronic Theses and Dissertations Center. 04 May 2015.

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Johnston, Alyssa "A Ternary Drug Delivery Complex to Target CD44 Over Expressing Cancerous Cell Lines." Electronic Thesis or Dissertation. Kent State University, 2012. https://etd.ohiolink.edu/

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