HER2 expression in breast cancer cells is downregulated upon active targeting by antibody-engineered multifunctional nanoparticles in mice

Fabio Corsi, Luisa Fiandra, Clara De Palma, Miriam Colombo, Serena Mazzucchelli, Paolo Verderio, Raffaele Allevi, Antonella Tosoni, Manuela Nebuloni, Emilio Clementi, Davide Prosperi

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)6383-6393
Number of pages11
JournalACS Nano
Volume5
Issue number8
DOIs
Publication statusPublished - Aug 23 2011

Keywords

  • breast cancer
  • imaging
  • ligand-receptor recognition
  • magnetic nanoparticles
  • theranostic agent
  • tumor targeting

ASJC Scopus subject areas

  • Engineering(all)
  • Materials Science(all)
  • Physics and Astronomy(all)

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