Abstract 3223: EGFR targeted iron-oxide nanoparticles for photodynamic therapy in head and neck cancer

Abstract

Abstract Photodynamic therapy (PDT) is a highly specific anti-cancer treatment modality for various cancers, particularly for recurrent cancers which fail to respond to conventional anti-cancer therapies. PDT has been developed for decades, but light-associated toxicity limits its clinical application. To improve the efficacy and reduce the toxicity of PDT, we developed a new targeted nanoparticle (NP) platform that combines a second-generation PDT drug, Pc 4, with a cancer targeting ligand and iron oxide (IO) NPs. Carboxyl functionalized IO NPs were first conjugated with an EGFR specific single chain fragment variable antibody (ScFv EGFR). PDT drug Pc 4 was then successfully encapsulated into the ligand-conjugated IO NPs to generate E-IO-Pc 4. Both in vitro and in vivo biodistribution and efficacy studies were then carried out to characterize this newly designed nanoparticlized PDT drug. An in vitro efficacy study using SRB assay on HNSCC cell lines showed both E-IO-Pc 4 and IO-Pc 4 had equal efficacy compared to free Pc 4, indicating that conjugated Pc 4 in IO NPs is as biologically active as free Pc 4. Our in vitro binding assay showed that at 4°C, targeted E-IO-Pc 4 had higher cell binding affinity than non-targeted IO-Pc 4 NPs ( p<0.001). An in vivo biodistribution study using a fluorescence imaging system indicated that both non-targeted IO-Pc 4 and targeted E-IO-Pc 4 NPs accumulated in xenograft tumors with a higher concentrations than non-formulated Pc 4 at 4 hour (p<0.01 for both nanoparticle drugs), 24 hour (p<0.01 for both nanoparticle drugs), and 48 hour (p<0.01 and p<0.005 for IO-Pc 4 and E-IO-Pc 4, respectively). A six-fold lower dose of equivalent Pc 4 than previously reported free formulated Pc 4 dose was used in the in vivo drug efficacy study using a nude mouse xenograft model. We found that both IO-Pc 4 and E-IO-Pc 4 inhibited HNSCC xenograft tumors growth more effectively than free Pc 4 (p<0.01 and p<0.001 for IO-Pc 4 and E-IO-Pc 4, respectively). Particularly, the targeted E-IO-Pc 4 NPs demonstrated a significantly higher inhibitory effect on tumor growth than non-targeted IO-Pc 4 NPs (p<0.005). These results suggest that the delivery of PDT agent Pc 4 by IO NPs can enhance its treatment efficacy and reduce its administrating dose. The targeted E-IO-Pc 4 NPs have great potential to serve as both imaging and PDT agent in the clinic. [This study was supported by NIH grants R01CA156775 (PI: Fei) and R21CA176684 (PI: Fei), Georgia Cancer Coalition Distinguished Clinicians and Scientists Awards (PIs: Fei and Chen),(PI: Shin), NIH SPORE P50 CA128613 (PI: Dong M Shin) and Emory Molecular and Translational Imaging Center (NIH P50CA128301)]. Citation Format: Dongsheng Wang, Xulei Qin, Guoqing Qian, Luma Halig, Baowei Fei, Zhengjia Chen, Zhuo Georgia Chen, Nabil F. Saba, Dong M. Shin, Hong Xu, Andrew Y. Wang. EGFR targeted iron-oxide nanoparticles for photodynamic therapy in head and neck cancer. [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 3223. doi:10.1158/1538-7445.AM2014-3223