Surface functionalization of superparamagnetic nanoparticles for the development of highly efficient magnetic resonance probe for macrophages

Abstract

In vivo magnetic resonance imaging (MRI) tracking of macrophages plays an important role in monitoring and understanding numerous human diseases with high macrophage activity. In this work, superparamagnetic iron oxide nanoparticles (SPIONs) of ∼12nm were surface-functionalized with poly(DL-lactic acid-co-malic acid) copolymer (PLMA) via a nanoprecipitation method. The r 1, r 2 and r 2/r 1 values of the PLMA-SPIONs obtained at a magnetic field of 3 T were 0.38, 196 and 516mM -1s -1, respectively. The high r 2/r 1 ratio can be expected to provide enhanced MR contrast. The PLMA-SPIONs were readily taken in by macrophages and the high iron uptake was confirmed via Prussian Blue staining and quantified by inductively coupled plasma mass spectrometry (ICP-MS). No significant cytotoxicity was found even at a high nanoparticle loading of 67.7pg Fe per cell. A linear relationship between R 2 and R2* values and the number of PLMA-SPIONs labeled cells was observed in vitro. As a result of the significantly higher R2* than R 2 effects, an in vitro detection threshold of about 2820 labeled cells was achieved with short labeling time and low nanoparticle concentration using a clinical 3 T MRI scanner. Thus, the PLMA-SPIONs can be potentially useful as magnetic resonance probes for targeting and tracking macrophages. Copyright © 2011 John Wiley & Sons, Ltd. Superparamagnetic iron oxide nanoparticles modified with poly(DL-lactic acid-co-malic acid) are biocompatible with a high r 2/r 1 ratio of 516 and are readily taken in by macrophages. The R2* effects of cell-bound nanoparticles outweigh R 2 effects. Detection of small amounts of labeled cells with high sensitivity is possible. Hence, these nanoparticles are potentially useful as magnetic resonance probe for targeting macrophages. © 2011 John Wiley & Sons, Ltd.