Integrinβ6-Targeted Immunoliposomes Mediate Tumor-Specific Drug Delivery and Enhance Therapeutic Efficacy in Colon Carcinoma

Purpose: Adjuvant chemotherapy is one of the significant treatments for colon cancer in clinic. However, it does not achieve the desired therapeutic efficacy, largely due to chemotherapeutic resistance. Integrinβ6 (ITGB6) is expressed in malignant colonic epithelia, but not in normal epithelia, and is associated with the progression, metastasis, and chemotherapeutic resistance of colon cancer. Accordingly, it is necessary to design therapeutic approaches for efficient and targeted drug delivery into ITGB6-positive cancer cells to improve chemotherapeutic efficacy in colon cancer. Experimental Design: PEGylated liposomes were employed to design ITGB6-targeted immunoliposomes, which have ITGB6 monoclonal antibodies (mAbs) conjugated. We evaluated the ITGB6-targeted immunoliposomes internalization into colon cancer cells and examined 5-fluorouracil (5-FU)–induced cellular apoptosis produced by ITGB6-targeted immunoliposomes+5-FU. In addition, the biodistribution and antitumor efficiency of ITGB6-targeted immunoliposomes were observed in vivo . Results: ITGB6-targeted immunoliposomes enhanced cellular internalization in ITGB6-positive colon cancer cells compared with liposomes. Furthermore, the ITGB6-targeted immunoliposome internalization was dependent on the ITGB6 expression level on cellular surface. ITGB6-targeted immunoliposomes decreased the 5-FU IC 50 more than 90% in HT-29 and SW480β6 cells relative to liposomes. Moreover, when loaded with 5-FU, ITGB6-targeted immunoliposomes produced an approximately 1.5-fold higher 5-FU–induced cellular apoptosis rate than liposomes. In vivo , the therapeutic activity of ITGB6-targeted immunoliposomes+5-FU was significantly superior, resulting in 25% to 35% reduction of tumor weight compared with 5-FU or liposomes+5-FU. Conclusions: ITGB6-targeted immunoliposomes provide a highly efficient approach for targeted drug delivery in colon cancer and thus offer the potential of a novel and promising anticancer strategy for clinical therapy. Clin Cancer Res; 21(5); 1183–95. ©2014 AACR .