Ovarian cancer cells targeting fluorescent-magnetic imaging dual-modal nanoprobe: from synthesis to imaging in vitro

Objective To fabricate manganese-doped carbon quantum dots (Mn-CDs) @anti-human epididymis protein 4 (HE4) monoclonal antibody (Mn-CDs@Anti-HE4 mAb) dual-modal fluorescent-magnetic nanoprobe for ovarian cancer cells targeting imaging, and evaluate its potential on fluorescent imaging and MRI. Methods Mn-CDs were synthesized at 150 ℃ with solvothermal method. The average diameter, fluorescent capability and MRI efficiency were determined. The cytotoxicity of Mn-CDs in vitro was evaluated by 3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay with HO-8910 ovarian cancer stem cells and EA.hy926 human umbilical vein endothelial cells. Mn-CDs@Anti-HE4 mAb was fabricated with condensation reaction and characterized by ultraviolet (UV) absorption spectra. Fluorescence imaging and MRI in vitro was performed for cancer cell-targeting study. One-way analysis of variance and the least significant difference t test were used to analyze the data. Results The Mn-CDs with diameter of (4.64±0.85) nm showed a well-defined spherical morphology. The fluorescent spectra of Mn-CDs exhibited a typical excitation-dependent behavior with an excitation maximum at 360 nm and emission maximum at 440 nm. The T1 relaxation rate was (3.26±0.04) mmol·L-1·s-1. The cytotoxicity tests in vitro showed that the survival rates of HO-8910 cells and EA.hy926 cells were both significantly different after treated with different concentrations of Mn-CDs (F=1 947.509, 260.174, both P 0.05), while the survival rates of the two kinds of cells were descended with the increasing of concentration within 3.0-4.5 mg/ml (P<0.05). Mn-CDs@Anti-HE4 mAb could target HO-8910 cells on fluorescence imaging and MRI. Conclusions Mn-CDs@Anti-HE4 mAb, with good potential on fluorescence imaging, MRI and targeting ability, is successfully synthesized. It may provide a new method for early diagnosis of ovarian cancer. Key words: Ovarian neoplasms; Tumor cells, cultured; Nanoparticles; Manganese; Quantum dots; Antibodies, monoclonal; Optical imaging; Magnetic resonance imaging