Superparamagnetic Nanoparticles with Phosphorescent Complexes as Hybrid Contrast Agents: Integration of MRI and PLIM

Rivas Aiello, M. B.; Kirse,, T. M.; Lavorato, G. C.; Maus, B.; Maisuls, I.; Kuberasivakumaran, S.; Ostendorp, S.; Hepp, A.; Holtkamp, M.; Winkler, E. L.; Karst, U.; Wilde, G.; Faber, C.; Vericat, C.; Strassert, C. A.

Abstract

Two different hybrid nanosystems are prepared by loading highly crystalline, monodisperse magnetite nanocubes (MNCs) with phosphorescent Pt(II) complexes (PtCxs). One involves the encapsulation of the hydrophobic PtCx1 within an amphiphilic comb polymer (MNC@poly(maleic anhydride-alt-1-octadecene) [PMAO]–PtCx1), whereas the other involves the direct binding of the hydrophilic PtCx2 to the surface of the MNC mediated by a ligand-exchange procedure (MNC@OH–PtCx2). Both systems are evaluated as potential candidates for multimodal imaging in magnetic resonance imaging (MRI) and photoluminescence lifetime imaging micro(spectro)scopy (PLIM). PLIM measurements on agarose phantoms demonstrate significantly longer excited-state lifetimes compared to the short-lived autofluorescence of biological background. Additionally, both nanosystems perform as effective MRI contrast agents (CAs): the r2* values are 3–4 times higher than for the commercial CA ferucarbotran. MNC@PMAO–PtCx1 particles also cause significant increases in r2. While the ligand exchange procedure efficiently anchors PtCxs to the MNC surface, the polymeric encapsulation ensures higher colloidal stability, contributing to differences in PLIM and MRI outcomes. In these results, the successful integration of two complementary noninvasive imaging modalities within a single nanosystem is confirmed, serving as the impetus for further investigation of such systems as advanced multimodal–multiscale imaging agents with dual orthogonal readouts.