Abstract 4475: IL-4 receptor-targeted delivery of liposomal doxorubicin and siRNA to tumor

Abstract

Abstract Targeted delivery of imaging agents and therapeutics to tumors would provide early detection and increased therapeutic efficacy against cancer. Using phage displayed-random peptide libraries, we have identified IL4RPep-1 (IL-4 receptor-binding peptide-1), CRKRLDRNC, that binds to IL-4 receptor (IL4R). IL4R is over-expressed on many types of cancer cells including lung cancer and breast cancer. Peptides have smaller size and in turn may exert better tissue penetration than bulky antibodies. IL4RPep-1 bound to H226 lung tumor cells that over-express IL4R, while little binding was observed in H460 lung tumor cells that express IL4R at low levels. When injected intravenously into nude mice bearing a subcutaneous H226 tumor, Cy7.5 near-infrared fluorescence (NIRF) dye-conjugated IL4RPep-1 selectively homed to tumor. IL4RPep-1-labeled liposomes containing doxorubicin showed more efficient anti-tumor growth activity than untargeted liposomes. In addition, IL4RPep-1-labeled, branched-type polyethyleneimine nanoparticles containing Bcl-xL siRNA more efficiently knocked down Bcl-xL expression and showed higher cytotoxic effect on cancer cells over-expressing IL4R than cancer cells expressing IL4R at low levels. These results suggest that IL4RPep-1 could be a useful probe for affinity-based imaging and drug delivery to tumor that over-expressing IL4R. Citation Format: Poongkavithai Vadevoo Sri Murugan, Gunassekaran Gowri Rangaswamy, Lianhua Chi, Guruprasath Padmanaban, Moon-Chang Baek, In-San Kim, Rang-Woon Park, Byung-Heon Lee. IL-4 receptor-targeted delivery of liposomal doxorubicin and siRNA to tumor. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4475. doi:10.1158/1538-7445.AM2014-4475