RESUMEN
New recombinant carriers-modular nanotransporters (MNTs)-with N-terminal ligand module to the epidermal growth factor receptor (EGFR) were developed and characterized. Human epidermal growth factor (hEGF) and antibody-like protein Z1907 were used as a ligand module. We demonstrated that MNTs are able to internalize in a receptor-specific manner into the target cancer cells and to accumulate in the target cell nuclei. Conjugation of MNTs with the Auger electron emitter 111In significantly enhanced the cytotoxic effect of 111In on the target cells. It was found that the transfer of EGF from the C-terminus to the N-terminus of the MNT enhanced the proliferation of target cells, whereas the use of Z1907 did not have a similar effect.
Asunto(s)
Factor de Crecimiento Epidérmico/química , Receptores ErbB/metabolismo , Proteínas Recombinantes/metabolismo , Antineoplásicos/farmacología , Línea Celular Tumoral , Núcleo Celular/metabolismo , Proliferación Celular , Sistemas de Liberación de Medicamentos , Humanos , Radioisótopos de Indio/química , Ligandos , Células MCF-7 , Unión Proteica , Dominios ProteicosRESUMEN
A new modular nanotransporter (MNT) for the delivery of anticancer agents into the nuclei of cells with folate receptor overexpression was created. An effective method for acceding labeling of this MNT with Auger electron emitter 111In has been developed. A significant therapeutic effect was observed after a single intratumoral injection of the new 111In-labeled MNT to mice grafted with human cervical carcinoma characterized by folate receptor overexpression.
