Development of a conjugate of magnetic nanoparticles with antibodies against GD 2, designed for the diagnostics of brain tumors

In tumors of neuroectodermal origin, a high level of expression of disialoganglioside GD 2 is observed, while in normal tissues its expression level is significantly lower, which makes GD 2 a promising target for the diagnostics of malignant neoplasms.

PURPOSE OF THE STUDY: was to synthesize and characterize the physicochemical properties of a laboratory sample of antiGD 2-mAbs@SPIONs, prepared on the basis of superparamagnetic nanoparticles, and intended for the diagnostics of malignant neoplasms of brain tumors.

MATERIALS AND METHODS: Superparamagnetic iron oxide nanoparticles (SPIONs) coated with carboxymethyldextran were synthesized using the method of co-precipitation in an aqueous medium. They were then conjugated with antibodies against GD 2 labeled with a fluorescent dye (fluorescein-5-maleimide). Next, the anti-GD 2-mAbs@SPIONs conjugate was purified by dialysis.

The concentration of iron, coating (carboxymethyl-dextran) and protein (antibodies against GD 2) in the resulting nanosuspension was measured using the thiocyanate method, by quantifying the reaction of the polymer with an antron reagent and by the Bradford method, respectively. Using dynamic light scattering, data on the surface charge of conjugates were obtained, their hydrodynamic size and the nature of dispersion were established. The analysis of MR-contrasting properties was carried out using the MRI method of a phantom sample on an NMR spectrometer.

The interaction of the anti-GD 2-mAbs@SPIONs conjugate with cells of the U 251 line (human glioblastoma) was recorded using confocal microscopy.

RESULTS. A laboratory sample of superparamagnetic nanoparticles anti-GD 2-mAbs@SPIONs recognizing disialoganglioside GD 2 on the membrane surface of cancer cells was synthesized and characterized using physicochemical methods. A specific accumulation of the drug in glioblastoma cells has been shown in comparison with unconjugated nanoparticles.

CONCLUSION. The specificity of the accumulation of magnetic conjugate in tumor cells gives hope for the possibility of using anti-GD 2-mAbs@SPIONs in the diagnostics of malignant neoplasms of the central nervous system, however, further research is needed.

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