Journal
ACS NANO
Volume 5, Issue 8, Pages 6383-6393Publisher
AMER CHEMICAL SOC
DOI: 10.1021/nn201570n
Keywords
magnetic nanoparticles; breast cancer; tumor targeting; imaging; ligand-receptor recognition; theranostic agent
Categories
Funding
- Assessorato alla Sanita
- Regione Lombardia
- Sacco Hospital
- Fondazione Romeo ed Enrica Invernizzi
- Italian Association for Cancer Research
- Centro di Microscopia Elettronica per lo sviluppo delle Nanotecnologie applicate alla medicina (CMENA. University of Milan)
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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.
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