RESUMEN
A water-soluble fluorescent aza-BODIPY platform (Wazaby) was prepared and functionalized by a polyazamacrocycle agent and a bioconjugable arm. The resulting fluorescent derivative was characterized and bioconjugated onto a trastuzumab monoclonal antibody as a vector. After bioconjugation, the imaging agent appeared to be stable in serum (>72 h at 37 °C) and specifically labeled HER-2-positive breast tumors slices. The bioconjugate was radiolabeled with [111In] indium and studied in vivo. The developed monomolecular multimodal imaging probe (MOMIP) is water-soluble and chemically and photochemically stable, emits in the near infrared (NIR) region (734 nm in aqueous media), and displays a good quantum yield of fluorescence (around 15%). Single-photon emission-computed tomography and fluorescence imaging have been performed in nude mice bearing HER2-overexpressing HCC1954 human breast cancer xenografts and have evidenced the good tumor targeting of the [111In] In bimodal agent. Finally, the proof of concept of using it as a new tool for fluorescence-guided surgery has been shown.
Asunto(s)
Compuestos de Boro/química , Neoplasias de la Mama/diagnóstico por imagen , Desarrollo de Medicamentos , Colorantes Fluorescentes/química , Imagen Óptica , Tomografía Computarizada de Emisión de Fotón Único , Animales , Anticuerpos Monoclonales/química , Compuestos de Boro/síntesis química , Relación Dosis-Respuesta a Droga , Femenino , Colorantes Fluorescentes/síntesis química , Células Hep G2 , Humanos , Neoplasias Mamarias Experimentales/diagnóstico por imagen , Ratones , Ratones Desnudos , Estructura Molecular , Solubilidad , Relación Estructura-Actividad , Agua/químicaRESUMEN
Three near-infrared (NIR-I) optical theranostic systems were synthesized, characterized and studied in vitro and in vivo. These original homo-bimetallic gold(I)-based aza-BODIPY complexes proved to be trackable through near-infrared optical imaging in cells and in mice. They display anti-proliferative properties in micromolar range against human and murine cancer cell lines (4T1, MDA-MB-231, CT26, and SW480). Moreover, the injection of the most promising theranostic agent in CT26 tumor-bearing BALB/c mice induced a significant anti-cancer activity.