| Summary: | 碩士 === 國立陽明大學 === 微生物及免疫學研究所 === 101 === Colorectal cancer (CRC) has became the most frequently encountered cancer and the third most common cause of cancer-related death in Taiwan since 2007. The cause of CRC mortality is mainly due to the resistance to treatment and the occurrence of distant metastasis, Unfortunately, proximately 45% CRC patients are diagnosed after metastasis. Recent evidences suggest that circulating tumor cell or cancer stem cells could contribute to tumor initiation and metastasis, and confers to drug resistance. Therefore, specifically targeting and killing of these cells could reduce the probability of recurrence. Previous studies have shown that Atherosclerotic plaque-specific peptide-1 (AP1) can high affinity bind to interleukin-4 receptor (IL-4R that is a tumor-promoting molecule and overexpress on CRC tissues. In this study, we used a novel doxorubicin-loaded liposome nanoparticle conjugated with AP1(Lipo-Dox-AP1) and established the IL-4Rstable expression cells (CT26-IL4R) and control cells (CT26-ctrl) to evaluate the treatment efficacy of novel nanoparticle in vitro and in vivo. First of all, immunohistochemistry analysis revealed that IL-4Rα were highly expressed in colorectal cancer tissue compared to normal tissue. Moreover, the AP1 peptide exhibited more bound to and be internalized into CT26-IL4R than CT26-ctrl. Furthermore, Lipo-Dox-AP1 showed a selective cytotoxicity to CT26-IL4R than CT26-ctrl. The Lipo-Dox-AP1 showed higher survival rate than Lipo-Dox or free doxorubicin though tumor inhibition ability was not significantly different in mice bearing CT26 cells. However, the Lipo-Dox-AP1 exhibited better tumor suppression ability than Lipo-Dox or free doxorubicin in mice bearing CT26-IL4R cells. Blood chemical analysis revealed that Lipo-DOX-AP1 was less toxic to kidney. In conclusion, we evaluate the AP1 is an excellent conjugated molecule that can enhance specifically binding to and uptake in cells and showed better therapeutic efficacy in tumor-bearing mice. Inhibition of CRC metastasis using Lipo-DOX-AP1 will be further investigated in orthotopic animal model.
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