Abstract 5487: A new generation of tumor targetable polymeric nanoparticles for cancer therapy and imaging

Abstract

Abstract Despite the significant progress in the development of anticancer technology, there is still no common cure for patients with malignant diseases. Conventional anticancer treatments are nonspecific to target killing of tumor cells, and always lead to systemic toxicity, causing undesirable severe side effects such as hair loss, damages to liver, kidney, and bone marrow. In order to achieve therapeutic levels of drug at the tumor site without damaging healthy organs and tissues, it is important to recognize the physiological differences between diseased and normal sites. Targeting drug delivery system is attracting increasing interest in research field to remove severe side effects and to increase reorganization of physiological differences. Polymeric nanoparticles can accumulate and extravasate within tumor tissue since their prolonged circulation by enhanced permeation and retention (EPR) effect, passive targeting system, which is achieved due to disorganized vascularization and defective vascular architecture induced in rapidly growing cancers. Even though passive targeting system shows moderate tumor therapeutic efficacy, active targeting drug delivery system has recently gained considerable attention to improve specificity. Especially, ligand/receptor-medicated targeting has emerged as a novel paradigm in the active targeting. Here, we have investigated active targeted polymeric nanoparticles by conjugation of tumor-specific homing peptide, AP-1 peptide, with modified glycol chitosan nanoparticles. Selection of peptides which show preferential binding to the target can be achieved by biopanning phage-displayed peptide libraries. Phage display technique is a promising tool for selecting peptides or proteins with specific binding properties from a lot of variants. AP-1 peptide can bind with interleukin-4 receptor which expressed on surface of several human cancer cells like H226 and MDA-MB231. Developed peptide-guided targetable polymeric nanoparticles show more specific binding and uptake as well as better therapeutic efficacy than net polymeric nanoparticles, passive targeted nanoparticles, which were confirmed with flowcytometry, immunofluorescence, histology, immunohitochemistry studies and animal experiments. In addition, they are better candidate as an imaging probe for cancer imaging and diagnosis than net polymeric nanoparticles. In conclusion, AP-1 peptide-conjugated chitosan nanoparticles are effective candidate as drug carrier and imaging probe for cancer therapy and imaging since AP-1 peptide induces the improvement of cell binding and uptake of nanoparticles. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5487.