Abstract 2188: Targeted delivery of pro-apoptotic peptide using ELP-based carrier for effective cancer therapy in various cancer model

Abstract

Abstract Therapeutic peptides classified as biopharmaceuticals have gained attention as a new generation of cancer therapeutics with enhanced efficiency and diminished toxicity. They often fail to have sufficient effects due to their unsatisfactory pharmacokinetic profiles, which include poor bioavailability, low stability, short half-life, and poor penetration across the biological membrane. Elastin-like polypeptide (ELP)-based drug delivery has been utilized for various applications including cancer therapies for many years. Genetic incorporation of internalization ligands and cell targeting peptides along with ELP polymer enhanced tumor accumulation and retention time as well as stability and activities of the drug conjugates. Herein, we described a unique delivery system comprised of genetically engineered ELP incorporated with multiple copies of IL-4 receptor targeting peptide (AP1) periodically and proapoptotic peptide (KLAKLAK)2 referred to as AP1-ELP-KLAK. It triggered thermal responsive self-assembly into a nanoparticle-like structure at physiological body temperature and stabilized its helical conformation, which is critical for its membrane disrupting activities. Increased IL-4 receptor specific cellular internalization was associated with the enhanced cytotoxic effect of (KLAKLAK)2 peptide. Additionally, multivalent presentation of targeting ligands by AP1-ELP-KLAK significantly enhanced intratumoral localization and prolonged the retention time compared to ELP-KLAK, non-targeted control. Systemic administration of AP1-ELP-KLAK significantly inhibited tumor growth by provoking cell apoptosis in MDA-MB231 breast cancer and B16F10 melanoma tumor xenograft models without any specific organ toxicity. Thus, our newly designed AP1-ELP-KLAK polymer nanoparticle is a promising candidate for effective cancer therapy and due to the simple preparative procedures of ELPs, this platform can be used as a good carrier for tumor-specific delivery of other therapeutics. Citation Format: Sarangthem Vijaya, Rang-Woon Park. Targeted delivery of pro-apoptotic peptide using ELP-based carrier for effective cancer therapy in various cancer model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2188. doi:10.1158/1538-7445.AM2017-2188