Abstract

Abstract Nanotechnologies are in development for monitoring drug delivery and therapeutic effect for cancer. However, tumor-targeted multifunctional nanoparticles for imaging of and therapy of lung cancer are not available. The Epidermal growth factor receptor (EGFR) is overexpressed in approximately 80% of non-small cell lung cancer (NSCLC) and is a target for novel therapeutics, however, the clinical results using EGFR inhibitors for NSCLC treatment had mixed results. These results indicate that EGFR expression or its mutational status is solely not a reliable marker to determine the outcome. Therefore, we have developed liposome (120nm) encapsulated with colloidal gold that are conjugated to therapeutic anti-EGFR antibodies (Katayama Chemical Industries Co. Ltd. Osaka, Japan) to determine the molecular specific imaging of NSCLC. The colloidal gold is used for optical imaging and the anti-EGFR antibody for therapy. In the present study, we investigated in vitro effect of these liposomes on EGFR-expressing (HCC827 and H1299) and EGFR-null (H520) NSCLC cells. EGFR-targeted liposome exhibited a strong antitumor effect on EGFR-expressing NSCLC cells. On the other hands, no significant growth inhibitory effects were observed on non-targeted liposome-treated cells. Intriguingly, treatment with EGFR-targeted liposome resulted in significantly higher cell death as compared with anti-EGFR antibody and liposome alone. Furthermore, reflected polarizing microscopy showed that the concentration of EGFR-targeted liposome bound to EGFR-expressing NSCLC cells increased, but EGFR-null cells did not. When EGFR was inhibited pharmacologically, the binding efficiency of EGFR-targeted liposome was attenuated on EGFR-expressing NSCLC cells. These findings indicate that EGFR-targeted liposome are selectively bound and delivered to EGFR expressing NSCLC cells but not the EGFR-null NSCLC cells. We are currently determining in vivo effect of EGFR-targeted liposome using subcutaneous HCC827 and H520 tumor models. Our findings demonstrated that EGFR-targeted liposome is a promising agent for therapy and molecular imaging of NSCLC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2904. doi:1538-7445.AM2012-2904

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