Surface engineered antifouling optomagnetic SPIONs for bimodal targeted imaging of pancreatic cancer cells

Abstract

Xiaohui Wang,1 Xiaohong Xing,1 Bingbo Zhang,1 Fengjun Liu,1 Yingsheng Cheng,2 Donglu Shi1,31Radiology Department of the Tenth People’s Hospital,The Institute for Biomedical Engineering and Nano Science, Tongji University School of Medicine, Shanghai, People’s Republic of China; 2Department of Radiology, Shanghai Sixth People’s Hospital, Shanghai Jiaotong University, Shanghai, People’s Republic of China; 3Materials Science and Engineering Program, Department of Mechanical and Materials Engineering, College of Engineering and Applied Science, University of Cincinnati, Cincinnati, OH, USAAbstract: Targeted imaging contrast agents for early pancreatic ductal adenocarcinoma diagnosis was developed using superparamagnetic iron oxide nanoparticles (SPIONs). For phase transfer of SPIONs, the hydrophobic SPIONs are first treated with tetrafluoroborate and then capped by bovine serum albumin (BSA) via ligand exchange. It was experimentally found that nitrosyl tetrafluoroborate pretreatment and proper structures of molecules are essential to the effective surface functionalization of SPIONs. Nonspecific binding was found to be significantly reduced by BSA surface functionalized hydrophobic SPIONs (BSA·SPIONs). The BSA·SPIONs were monodispersed with an average size of approximately 18.0 nm and stable in a wide pH range and various ionic strengths even after 7 days of storage. The longitudinal and transverse proton relaxation rate (r1, r2) values of the BSA·SPIONs were determined to be 11.6 and 154.2 s-1 per mM of Fe3+ respectively. The r2/r1 ratio of 13.3 ensured its application as the T2-weighted magnetic resonance imaging contrast agents. When conjugated with near-infrared fluorescent dye and monoclonal antibody, the dyeBSA·SPION-monoclonal antibody bioconjugates showed excellent targeting capability with minimal nonspecific binding in the bimodal imaging of pancreatic cancer cells. The experimental approach is facile, environmentally benign, and straightforward, which presents great promise in early cancer diagnosis.Keywords: superparamagnetic iron oxide nanoparticles, BSA, bimodal imaging, MRI, targeted imaging