| Summary: | 碩士 === 國立臺灣大學 === 生化科技學系 === 105 === In tradition, drugs for cancer treatment always belong to a dump release system. Furthermore, people are devoted to developing the new drug delivery for cancer therapy. Recently, liposomes, primarily composed of phospholipids, are the major drug delivery system. However, liposomes still have some disadvantages as follows. In recent years, there are many research for find new drug delivery, and the ferritin is the one of them.
Ferritin is composed of 24 subunits and able to self-assemble to form a nanocage structure with external and internal diameters of 12 and 8 nm, respectively. Ferritin can be easily modified and conjugated with various molecules onto the surface, including dye, peptides, siRNA or antibodies etc. the cavity of ferritin can be loaded drugs.
Recent studies demonstrated RGD-modified ferritin had potential in cancer diagnosis and therapy. The RGD peptide has high affinity to integrin αVβ3, a tumor angiogenesis biomarker, and is currently applied to clinical cancer imaging. However, the RGD peptide has disadvantages that the peptide also targets to endothelial cells, leading to stimulation of tumor growth and angiogenesis.
Hence, in this study, we wanted to construct a new drug delivery and applied on molecular imaging and cancer therapy. We intended to set up the integrin-targeted ferritin with the DGEA (Asp-Gly-Glu-Ala) peptide which has high affinity to integrin α2β1. In the thesis, we not only made the construct of DGEA-ferritin but also tried the 2xDGEA-ferritin to assess the effect of increasing the copy number of DGEA on the surface of ferritins. Next, we estimated the tumor targeting ability of DGEA-ferritin and 2xDGEA-ferritin on U-87 MG, glioblastoma cell line, or PC-3, human prostate cancer cell line, by incubating cells with FITC-labeled protein. After confirming that proteins could recognize cancer cells through the DGEA peptide, we loaded the doxorubicin into 2xDGEA-ferritin. Through the MTT assay, we demonstrated that the 2xDGEA-ferritin could kill cancer cells and improved drug efficiency, which could use less amount of doxorubicin than free doxorubicin to achieve the same cellular toxicity effect. In the future, we will do in vivo experiments to confirm the potential of developing this drug delivery. If the system succeeds, it will be a new, safe and efficient technology and has great potential in clinical application. Furthermore, multiple peptides could be constructed on the ferritin or other drugs be loaded into the ferritin, and apply these modified-ferritins on molecular imaging and cancer therapy.
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