Development of a Mucin4-Targeting SPIO Contrast Agent for Effective Detection of Pancreatic Tumor Cells in Vitro and in Vivo

Abstract

In search of a unique and reliable contrast agent targeting pancreatic adenocarcinoma, new multifunctional nanoparticles (MnMEIO-silane-NH2-(MUC4)-mPEG NPs) were successfully developed in this study. Mucin4-expression levels were determined through different imaging studies in a panel of pancreatic tumor cells (HPAC, BxPC-3, and Panc-1) both in vitro and in vivo studies. The in vitro T-2-weighted MR imaging study in HPAC and Panc-1 tumor cells treated with NPs showed -89.1 +/- 5.7% and -0.9 +/- 0.2% contrast enhancement, whereas in in vivo study, it is found to be -81.5 +/- 4.5% versus -19.6 +/- 5.2% (24 h postinjection, 7.0 T), respectively. The T-2-weighted MR and optical imaging studies revealed that the novel agent can specifically and effectively target to mucin4-expressing tumors in nude mice. Hence, it is suggested that MnMEIO-silane-NH2-(MUC4)-mPEG NPs are able to provide an efficient and targeted delivery of MUC4 antibodies to mucin4-expressing pancreatic tumors.