Abstract 4115: Comparison of IL-4 receptor targeting elastin-like polypeptide based on size and structure

Abstract

Abstract For novel drug delivery systems, in order to improve clinical outcomes clear optimization of size, shape, multifuntionality, and site-specificity are highly considered. As molecular size significantly influenced the biodistribution, precise control of molecular sizes must be considered for optimum targeting effect in cancer therapy. Elastin like polypeptide (ELP), has been utilized as an attractive vehicle for cancer therapy as it provide unparalleled control over sequence and structure in genetic level thereby allowing generation of various polymers with defined architectures and functional properties. In this study, we designed various multivalent elastin-like polypeptide based tumor targeting polymer in which multiple copies of IL-4 receptor (IL-4R) targeting ligands, AP1 peptide were subjected into ELP polymer backbone periodically to enhance affinity and avidity towards IL-4R- highly expressed tumor cells. Several ELP with different molecular sizes and structure from unimer to micelle forming polymer have been designed to investigate the pattern of accumulation in tumor, as well as their bio-distribution in vivo. Different percentage of cell binding and uptake depend on size, number of targeting peptides, or based on unimer compared with micelle were determined. The high molecular weight AP1-ELP showed superior binding activity with faster entry and efficiently processed in the IL-4R dependent endocytic pathway compared to low molecular weight polypeptides. In addition the high molecular weight, micelle forming AP1-ELP displayed better tumor penetration and extensive retention in tumor tissue with decrease non-specific accumulation in vital organs compared to low molecular weight AP1-ELP in xenograft model. It was suggested that superior binding activities shown by A86 and A100 may depends on multiple presentation of ligands upon transition to micelle like structure rather than increased number of targeting ligands and molecular weight. Thus this study have significance in demonstrating different pattern underlying unimer and micelle forming ELP mediated tumor targeting as well as biodistribution in vivo. Citation Format: Boyeon Seo, Vijaya Sarangthem, Aena Yi, Rang-Woon Park. Comparison of IL-4 receptor targeting elastin-like polypeptide based on size and structure [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4115.