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J Control Release ; 258: 196-207, 2017 07 28.
Artículo en Inglés | MEDLINE | ID: mdl-28445743

RESUMEN

The purpose of this research was to investigate the effectiveness of epidermal growth factor receptor (EGFR) targeted micelles loaded with IR-780 (Cetuximab/IR-780/micelles) for generating tumor targeting, multimodal images, and photothermal therapy (PTT). We initially studied the cellular uptake of these micelles using the HCT-116 and SW-620 cell lines. HCT-116 (high expression of EGFR) and SW-620 (low expression of EGFR) cell lines were used to examine biodistribution and antitumor effects of Cetuximab/IR-780/micelles. Time-lapse near-IR fluorescence (NIRF) images also indicated the highest IR-780 accumulation from Cetuximab/IR-780/micelles in HCT-116 tumors (p<0.05). HCT-116 tumors in tumor-bearing mice exhibited significantly higher accumulations of Cetuximab/IR-780/111In-micelles than SW-620 tumors in Micro-SPECT/CT imaging and biodistribution studies (p<0.05). Dual-radioisotope Nano-SPECT/CT imaging of Cetuximab/131I-IR-780/111In-micelles demonstrated simultaneous high accumulation of both IR-780 and micelles in HCT-116 tumors, but not in SW-620 tumors. Regarding antitumor effects, following the Cetuximab/IR-780/micelles with PPT on day 6, all HCT-116 tumor-bearing mice were cured. In contrast, SW-620 tumors relapsed at 13days after treatment. In summary, we expect that the Cetuximab/IR-780/micelles could enhance the antitumor effects by PTT in EGFR overexpression colorectal cancers through effective drug delivery nanoparticles.


Asunto(s)
Antineoplásicos Inmunológicos/administración & dosificación , Cetuximab/administración & dosificación , Neoplasias Colorrectales/terapia , Sistemas de Liberación de Medicamentos , Indoles/administración & dosificación , Animales , Antineoplásicos Inmunológicos/farmacocinética , Antineoplásicos Inmunológicos/uso terapéutico , Autorradiografía , Cetuximab/farmacocinética , Cetuximab/uso terapéutico , Neoplasias Colorrectales/diagnóstico por imagen , Neoplasias Colorrectales/metabolismo , Receptores ErbB/metabolismo , Femenino , Células HCT116 , Humanos , Hipertermia Inducida/métodos , Indoles/farmacocinética , Indoles/uso terapéutico , Ratones Desnudos , Micelas , Fototerapia/métodos , Distribución Tisular , Tomografía Computarizada de Emisión de Fotón Único
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