HER2 Expression in Breast Cancer Cells Is Downregulated Upon Active Targeting by Antibody-Engineered Multifunctional Nanoparticles in Mice

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 rela...

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Bibliographic Details
Published in:ACS nano 2011-08, Vol.5 (8), p.6383-6393
Main Authors: Corsi, Fabio, Fiandra, Luisa, De Palma, Clara, Colombo, Miriam, Mazzucchelli, Serena, Verderio, Paolo, Allevi, Raffaele, Tosoni, Antonella, Nebuloni, Manuela, Clementi, Emilio, Prosperi, Davide
Format: Article
Language:English
Subjects:
Animals
Antibodies, Monoclonal, Humanized - chemistry
Antineoplastic Agents - metabolism
Antineoplastic Agents - pharmacokinetics
Antineoplastic Agents - pharmacology
Antineoplastic Agents - toxicity
Biological Transport
Biomedical materials
Breast Neoplasms - diagnosis
Breast Neoplasms - genetics
Breast Neoplasms - metabolism
Breast Neoplasms - pathology
Cancer
Cell Line, Tumor
Down-Regulation - drug effects
Engineering
Female
Humans
In vivo testing
In vivo tests
Magnetic Resonance Imaging
Mice
Nanoparticles
Nanoparticles - chemistry
Nanostructure
Receptor, ErbB-2 - metabolism
Surgical implants
Trastuzumab
Tumors
Xenograft Model Antitumor Assays
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Summary: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.
ISSN:1936-0851
1936-086X
DOI:10.1021/nn201570n