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ACS Nano ; 13(12): 13884-13898, 2019 12 24.
Artículo en Inglés | MEDLINE | ID: mdl-31730332

RESUMEN

Cancer vaccines initiate antitumor responses in a subset of patients, but the lack of clinically meaningful biomarkers to predict treatment response limits their development. Here, we design multifunctional RNA-loaded magnetic liposomes to initiate potent antitumor immunity and function as an early biomarker of treatment response. These particles activate dendritic cells (DCs) more effectively than electroporation, leading to superior inhibition of tumor growth in treatment models. Inclusion of iron oxide enhances DC transfection and enables tracking of DC migration with magnetic resonance imaging (MRI). We show that T2*-weighted MRI intensity in lymph nodes is a strong correlation of DC trafficking and is an early predictor of antitumor response. In preclinical tumor models, MRI-predicted "responders" identified 2 days after vaccination had significantly smaller tumors 2-5 weeks after treatment and lived 73% longer than MRI-predicted "nonresponders". These studies therefore provide a simple, scalable nanoparticle formulation to generate robust antitumor immune responses and predict individual treatment outcome with MRI.


Asunto(s)
Antineoplásicos/farmacología , Células Dendríticas/metabolismo , Imagen por Resonancia Magnética , Nanopartículas de Magnetita/química , Animales , Biomarcadores de Tumor/metabolismo , Vacunas contra el Cáncer/inmunología , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Rastreo Celular , Células Dendríticas/efectos de los fármacos , Electroporación , Compuestos Férricos/química , Nanopartículas de Magnetita/ultraestructura , Ratones Endogámicos C57BL , Transfección
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