Subcellular destiny of targeted nanoparticles in cancer cells within living organisms is still an open matter of debate. By in vivo and ex vivo experiments on tumor-bearing mice treated with antibody-engineered magnetofluorescent nanocrystals, in which we combined fluorescence imaging, magnetic relaxation, and trasmission electron microscopy approaches, we provide evidence that nanoparticles are effectively delivered to the tumor by active targeting. These nanocrystals were demonstrated to enable contrast enhancement of the tumor in magnetic resonance imaging. In addition, we were able to discriminate between the fate of the organic corona and the metallic core upon cell internalization. Accurate immunohistochemical analysis confirmed that hybrid nanoparticle endocytosis is mediated by the complex formation with HER2 receptor, leading to a substantial downregulation of HER2 protein expression on the cell surface. These results provide a direct insight into the pathway of internalization and degradation of targeted hybrid nanoparticles in cancer cells in vivo and suggest a potential application of this immunotheranostic nanoagent in neoadjuvant therapy of cancer.
HER2 expression in breast cancer cells is downregulated upon active targeting by antibody-engineered multifunctional nanoparticles in mice / F. Corsi, L. Fiandra, C. De Palma, M. Colombo, S. Mazzucchelli, P. Verderio, R. Allevi, A. Tosoni, M. Nebuloni, E. Clementi, D. Prosperi. - In: ACS NANO. - ISSN 1936-0851. - 5:8(2011 Aug), pp. 6383-6393.
|Titolo:||HER2 expression in breast cancer cells is downregulated upon active targeting by antibody-engineered multifunctional nanoparticles in mice|
CORSI, FABIO RUGGERO MARIA (Primo)
CLEMENTI, EMILIO GIUSEPPE IGNAZIO (Penultimo)
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
Settore MED/18 - Chirurgia Generale
Settore MED/08 - Anatomia Patologica
Settore BIO/10 - Biochimica
Settore BIO/13 - Biologia Applicata
Settore BIO/12 - Biochimica Clinica e Biologia Molecolare Clinica
|Data di pubblicazione:||ago-2011|
|Centro di ricerca:||Centro di Ricerca Convenzionato di Microscopia Elettronica per lo Sviluppo delle Nanotecnologie Applicate alla Medicina|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1021/nn201570n|
|Appare nelle tipologie:||01 - Articolo su periodico|