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Updated: May 30, 2026
Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?
Published on: June 13, 2014
HER2 expression in breast cancer cells is downregulated upon active targeting by antibody-engineered multifunctional
Fabio Corsi1, Luisa Fiandra, Clara De Palma
1Dipartimento di Scienze Cliniche Luigi Sacco, Università di Milano, Ospedale L. Sacco, via G.B. Grassi 74, 20157 Milano, Italy.
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.
Insights
Targeted nanoparticles effectively reach tumors in mice via active targeting. This study clarifies their cellular fate and suggests potential for neoadjuvant cancer therapy.
Area of Science:
- Nanotechnology
- Oncology
- Biomedical Imaging
Background:
- The intracellular fate of targeted nanoparticles in cancer cells remains poorly understood.
- Understanding nanoparticle behavior is crucial for developing effective cancer therapies.
Purpose of the Study:
- To investigate the in vivo subcellular destiny of antibody-engineered magnetofluorescent nanocrystals in tumor-bearing mice.
- To evaluate the potential of these nanoparticles as an immunotheranostic agent for cancer treatment.
Main Methods:
- In vivo and ex vivo experiments utilizing antibody-engineered magnetofluorescent nanocrystals.
- Combined approaches including fluorescence imaging, magnetic relaxation, and transmission electron microscopy.
- Immunohistochemical analysis to confirm receptor-mediated endocytosis and HER2 downregulation.
Main Results:
- Nanoparticles demonstrated effective tumor delivery through active targeting.
- Enabled contrast enhancement in magnetic resonance imaging (MRI) for tumor visualization.
- Differentiated the fate of the organic corona and metallic core post-cell internalization.
- Confirmed HER2 receptor-mediated endocytosis, leading to HER2 protein downregulation.
Conclusions:
- Provided direct insights into the internalization and degradation pathways of targeted nanoparticles in cancer cells.
- Suggests potential application of this immunotheranostic nanoagent in neoadjuvant cancer therapy.
