LAUSR

Abstract A new theranostic ultrasmall superparamagnetic iron oxide nanoparticle (USPIONP)—consisting of an iron oxide nanoparticle (IONP) core, amphiphilic poly(aspartic acid) graft copolymer (P), and a model anticancer drug, epirubicin (EPI)—was developed and characterized. The graft copolymer P, poly(2-hydroxyethylaspartamide)-mPEG-C16, was synthesized by a polysuccinimide ring-opening reaction. The P-IONP, the IONP core of which was coated with polymer P, was synthesized using a co-precipitation method. The P-IONP was a USPIONP with an IONP core of diameter 6–9 nm and a hydrodynamic diameter of 41 nm. The EPI-loaded P-IONP (EPI-P-IONP) had a hydrodynamic diameter of 53 nm. The remarkably high relaxivity, r2, of 605.5 s−1 mM−1 of EPI-P-IONP corresponded to magnetic resonance contrast enhancement 2.7-fold that of a commercial contrast agent. The EPI encapsulation efficiency was 81%, and EPI was released from EPI-P-IONP in a sustained manner. P-IONP had negligible cytotoxicity against HeLa cells, while cytotoxicity increased in an EPI-dose-dependent manner after 4 h incubation with EPI-P-IONP. Cellular uptake of EPI from EPI-P-IONP was comparable to that of free EPI, as determined by flow cytometry. Confocal microscopy confirmed nuclear uptake of EPI released from EPI-P-IONP. These results suggest that the P-IONP has potential as an imaging agent and a therapeutic agent, and thus as a theranostic agent.