Transferrin-targeted magnetic/fluorescence micelles as a specific bi-functional nanoprobe for imaging liver tumor

Abstract

In order to delineate the location of the tumor both before and during operation, we developed targeted bi-functional polymeric micelles for magnetic resonance (MR) and fluorescence imaging in liver tumors. Hydrophobic superparamagnetic iron oxide nanoparticles (SPIONs) were loaded into the polymeric micelles through self-assembly of an amphiphilic block copolymer poly(ethylene glycol)-poly(ϵ-caprolactone). After, transferrin (Tf) and near-infrared fluorescence molecule Cy5.5 were conjugated onto the surface of the polymeric micelles to obtain the nanosized probe SPIO@PEG-b-PCL-Tf/Cy5.5 (SPPTC). Imaging capabilities of this nanoprobe were evaluated both in vitro and in vivo. The accumulation of SPPTC in HepG2 cells increased over SPIO@PEG-b-PCL-Cy5.5 (SPPC) by confocal microscopy. The targeted nanoprobe SPPTC possessed favorable properties on the MR and fluorescence imaging both in vitro and in vivo. The MTT results showed that the nanoprobes were well tolerated. SPPTC had the potential for pre-operation evaluation and intra-operation navigation of tumors in clinic.

Keywords: Fluorescence imaging; Liver tumor; Magnetic resonance imaging; Micelle; Target.

Figure 1

Characterization of SPPTC. TEM images of SPIO (a); TEM images of SPPTC through negative staining (b); hydrodynamic size distribution of SPPTC about 196 nm with PDI 0.168 (c). The saturation magnetizations (Ms) of SPPTC was 85.4 emu/g Fe at 300 K (d).

Figure 2

Magnetic and fluorescent properties of SPPTC. The r2 of SPPTC is 196.5 mM⁻¹ s⁻¹ and the r2 of SPPC is 219.1 mM⁻¹ s⁻¹ at 300 K respectively (a); the correlation between fluorescence intensity and the concentration of the nanoprobe (b).

Figure 3

The uptake of SPPC or SPPTC in HepG2 cell at different concentrations (Fe). Detected through MRI (a); detected by confocal microscope (b).

Figure 4

Fluorescence imaging of SPPTC in mice bearing the subcutaneous tumor at different time points. Top row, injected with SPPC; bottom row, injected with SPPTC.

Figure 5

T2-weighted MR imaging and Prussian blue staining.In vivo T2-weighted MR imaging before and after intravenous injection of SPPC or SPPTC (a); the histological sections of tumor with Prussian blue staining (b).

Figure 6

Viabilities of HL7702 cells treated with SPPTC.