Selective Targeting of Folate Receptor Expressing Cancer Cells Through the use of siRNA Gold Nanoparticle Complexes
Date of Award
Honors College Thesis
Chemistry and Biochemistry
Small interfering RNA, siRNA, is considered a next generation therapeutic agent in the treatment of cancer. However, siRNA has many challenges that must be overcome before it is suitable for medical purposes. This includes its unfavorable negative charge and its instability in serums which makes direct delivery impossible due to the rapid degradation of siRNA in biological systems. To accommodate the siRNA and gain the ability to use it as a therapeutic agent, it must first be encased in a complex that can deliver it to its intended target. Gold nanoparticles are a possible delivery agent for siRNA due to the ease of synthesis and modification to the complex and its nontoxic nature. This project aims to make a tumor specific gold nanoparticle complex that utilizes folic acid receptors that are present on certain cancer types and exploit this feature to selectively target these cancers and knockdown the synthesis of ribonucleotide reductase using siRNA. The complex was synthesized using a layer-by-layer method. The citrate stabilized gold nanoparticle serves as the core of the nanoplex which is then used as a base to add sequential layers to form the final complex of AuMUA/PEI/tRNA/PEI. The final product and the individual layers were characterized to ensure that each layer was added onto the complex. In order to characterize the nanoplexes, UV-vis spectroscopy, dynamic light scattering, and zeta potential were continually tested for each layer and the final product. Future work on this project should include studies into targeted siRNA delivery and cellular function such as delivery efficiency, gene knockdown efficiency, and effects on cell growth and cell death.
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Hamilton, Chandler L., "Selective Targeting of Folate Receptor Expressing Cancer Cells Through the use of siRNA Gold Nanoparticle Complexes" (2015). Honors Theses. 463.
Available for download on Tuesday, March 02, 2219