| Summary: | 碩士 === 國立成功大學 === 口腔醫學研究所 === 98 === ANGINEX is an artificial beta-sheet peptide composed of 33 amino acids. It inhibits vascular endothelial cell growth in vitro and tumor growth in vivo by targeting galectin-1 on the tumor associate vascular endothelial cells. Galectin-1 is overexpressed at the invasive front of oral carcinoma and oral cancer-associated vascular endothelial cells. In this study, we wanted to synthesize ANGINEX-conjugated nanoparticles to develop tumor-targeted nanoparticles for oral cancer imaging and therapy. First, we constructed ANGINEX DNA sequence into a pET-28a plasmid for recombinant ANGINEX protein production. We observed that like other anti-angiogenesis peptides, ANGINEX also carries the activity of bacteria proliferation inhibition. Even though we can see the ANGINEX appeared at the bacteria lysate, the ANGINEX concentration is not sufficient to support the following experiments. Therefore, we further used the synthetic ANGINEX for the following experiments. Next, ANGINEX-conjugated nanoparticles (ANG-Fe@) have been synthesized through self-assembly of hexahistidine tag on recombinant ANGINEX to nickel nitrilotriacetate (Ni-NTA) coated Fe3O4 nanoparticles. On the other hand, we have isolated a murine oral cancer cell line, named W1ms, from 4-NQO carcinogen feeding B6 mice. We have subcutaneously injected this cell line into the posterior flank and the tongue of SCID and B6 mice trying to induce experimental mice oral cancer models. After two months of implantation, we found W1ms cells failed to form tumor in both murine systems. Hence, we evaluated the tumor targeting and inhibiting abilities of ANG-Fe@ by using human oral cancer OC2 tumor mice model.
On the tumor bearing SCID mice, the ANG-Fe@ could induce a strong negative signal on liver and kidney on the MRI scanning. We do not found a strong negative signal in the tumor position. It might be due to the over absorption from the liver and kidney, resulting a low concentration of ANG-Fe@ in the tumor site. ANGINEX targets the endothelial cell, some of the endothelial cell over expressing Galectin-1 might also being targeted by the ANG-Fe@ thus reduce the negative signal of the tumor. To increase the tumor targeting ability of the nano-particle conjugated protein or try conjugate multiple peptide to increase the combination of the tumor receptors through the different peptides, also keep lower the absorption of the liver, kidney and the immune system. The peptide conjugated nanoparticle in the MRI imaging developing system could be a high precision way in the future medical bio-imaging technique.
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