Nonpolymeric surface-coated iron oxide nanoparticles for in vivo molecular imaging: biodegradation, biocompatibility, and multiplatform.

Chang-Moon Lee, Su-Jin Cheong, Eun-Mi Kim, Seok Tae Lim, Yong Yeon Jeong, Myung-Hee Sohn, Hwan-Jeong Jeong

Index: J. Nucl. Med. 54(11) , 1974-80, (2013)

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Abstract

A new approach to the surface engineering of superparamagnetic iron oxide nanoparticles (SPIONs) may encourage their development for clinical use. In this study, we demonstrated that nonpolymeric surface modification of SPIONs has the potential to be an advanced biocompatible contrast agent for biomedical applications, including diagnostic imaging in vivo.Adenosine triphosphate (ATP), which is an innate biomaterial derived from the body, was coated onto the surface of SPIONs. An in vivo degradation study of ATP-coated SPIONs (ATP@SPIONs) was performed for 28 d. To diminish phagocytosis, ATP@SPIONs were surface-modified with gluconic acid. We next studied the ability of the SPIONs to serve as a specific targeted contrast agent after conjugation of cMet-binding peptide. The SPIONs were conjugated with Cy5.5 and labeled with (125)I for multimodality imaging. In vivo and in vitro tumor-targeted binding studies were performed on U87MG cells or a U87MG tumor model using animal SPECT/CT, an optical imaging system, and a 1.5-T clinical MR scanner.ATP@SPIONs showed rapid degradation in vivo and in vitro, compared with ferumoxides. ATP@SPIONs modified with gluconic acid reduced phagocytic uptake, showed improved biodistribution, and provided good targetability in vivo. The gluconic acid-conjugated ATP@SPIONs, when conjugated with cMet-binding peptide, were successfully visualized on the U87MG tumors implanted in mice via multimodality imaging.We suggest that ATP@SPIONs can be used as a multiplatform to target a region of interest in molecular imaging. When we consider the biocompatibility of contrast agents in vivo, ATP@SPIONs are superior to polymeric surface-modified SPIONs.