Biocompatible Nanocomplexes for Molecular Targeted MRI Contrast Agent

Zhijin Chen,Zaijun Lu,Dexin Yu,Shaojie Wang,Na Zhang,Chunhong Ma

doi:10.1007/s11671-009-9286-x

Abstract

Accurate diagnosis in early stage is vital for the treatment of Hepatocellular carcinoma. The aim of this study was to investigate the potential of poly lactic acid–polyethylene glycol/gadolinium–diethylenetriamine-pentaacetic acid (PLA–PEG/Gd–DTPA) nanocomplexes using as biocompatible molecular magnetic resonance imaging (MRI) contrast agent. The PLA–PEG/Gd–DTPA nanocomplexes were obtained using self-assembly nanotechnology by incubation of PLA–PEG nanoparticles and the commercial contrast agent, Gd–DTPA. The physicochemical properties of nanocomplexes were measured by atomic force microscopy and photon correlation spectroscopy. The T1-weighted MR images of the nanocomplexes were obtained in a 3.0 T clinical MR imager. The stability study was carried out in human plasma and the distribution in vivo was investigated in rats. The mean size of the PLA–PEG/Gd–DTPA nanocomplexes was 187.9 ± 2.30 nm, and the polydispersity index was 0.108, and the zeta potential was −12.36 ± 3.58 mV. The results of MRI test confirmed that the PLA–PEG/Gd–DTPA nanocomplexes possessed the ability of MRI, and the direct correlation between the MRI imaging intensities and the nano-complex concentrations was observed (r = 0.987). The signal intensity was still stable within 2 h after incubation of the nanocomplexes in human plasma. The nanocomplexes gave much better image contrast effects and longer stagnation time than that of commercial contrast agent in rat liver. A dose of 0.04 mmol of gadolinium per kilogram of body weight was sufficient to increase the MRI imaging intensities in rat livers by five-fold compared with the commercial Gd–DTPA. PLA–PEG/Gd–DTPA nanocomplexes could be prepared easily with small particle sizes. The nanocomplexes had high plasma stability, better image contrast effect, and liver targeting property. These results indicated that the PLA–PEG/Gd–DTPA nanocomplexes might be potential as molecular targeted imaging contrast agent.

Highlights

The nanocomplexes had high plasma stability, better image contrast effect, and liver targeting property. These results indicated that the PLA–PEG/Gd–DTPA nanocomplexes might be potential as molecular targeted imaging contrast agent
The size of PLA–PEG and nanocomplexes was 56 and 70 nm, respectively, in the Atomic Force Microscopy Imaging (AFM) image, which was different from that observed by Photon Correlation Spectroscopy (PCS)
The particles within the 150–200 nm range were found to be longest circulating [19, 20], and so the PLA–PEG/Gd–DTPA nanocomplexes, with sizes around 200 nm, could be interesting to reach the loose junctions of the endothelium of cancer or infectious foci, considering the mean sizes measured by PCS

Summary

Introduction

Ma Department of Radiology Medicine, Affiliated Qilu Hospital, Shandong University, 44 Wenhua Xi Road, 250012 Ji’nan, People’s Republic of China. Hepatocellular carcinoma (HCC) is one of the most dreaded diseases in the world, which brings dramatic increases in morbidity and mortality both in the developed and developing countries. Accurate diagnosis in early stage is vital for the treatment of patients. Routine screening strategies such as ultrasound every 6 months have been recommended for early detection in patients with liver cirrhosis to detect HCC at earlier stage. Magnetic resonance imaging (MRI) is one of the most useful technologies in the field of diagnostic imaging [1]. The sensitivity and specificity of conventional MRI are far from satisfactory. The development of molecular imaging provide an unprecedented opportunity for the diagnostic detection rate of HCC

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