Identification of Oral Cancer-Targeted Peptides by in vivo Phage Display and Development of Ligand-Targeted Therapy for Oral Cacncer
| Autor: | Szu-Yao Kuo, 郭思堯 |
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| Rok vydání: | 2004 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 92 Oral cancer is a common cancer among Chinese living and ranks fourth in the mortality rate of male cancer patients in Taiwan. Cytotoxic chemotherapy or radiotherapy is major treatment as cancer therapies and is limited by serious side effects because therapies are not selective for malignant cells. Ligand-targeted therapy affords tumor specificity and limited toxicity and will promise new therapies to treat oral cancer. In vivo phage display is a powerful tool for the discovery of ligands that selectively home to tumor. In this study, we used this method to identify specific peptides that could home to the Severe combined immunodeficiency (SCID) mice bearing oral cancer xenograft. Several phage clones selected in this manner homed to the oral cancer 12–40 times more than to control organs. Unselected control phage did not show this preference. Synthetic peptide PIVO-2, corresponded to IVO-2 phage displayed peptide sequence, was shown to inhibit the homing activity completely when co-injected into mice with the phage. To determine the efficacy of the tumor-homing peptide PIVO-2 for improvement the therapeutic index, systemic treatment of oral cancer bearing mice with doxorubicin-loaded liposome (LD) and peptide-conjugated LD (LD-PIVO-2) was performed. The mice showed significantly smaller tumor mass when we treated with the LD-PIVO-2 than LD only. LD-PIVO-2 treated mice have 100% survival rate but LD treated mice only have 33.3% survival rate. These results indicate that PIVO-2 peptide enhanced the efficacy of the drug against oral cancer xenografts in SCID mice and suggest that this peptide has a strong clinical potential for drug delivery guider to treat oral cancer. We also developed ligand-targeted therapy using LD conjugated to angiostatin and RGD peptide. We found that the conjugation of LD with angiostatin or RGD peptide decrease the toxicity of cancer therapy to the tumor-bearing mice. This approach may provide a new strategy for the purpose of ligand-targeted therapy or anti-angiogenic therapy for solid tumors. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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