title: HER2 expression in breast cancer cells is downregulated upon active targeting by antibody-engineered multifunctional nanoparticles in mice.
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.
authors.affiliation: Dipartimento di Scienze Cliniche Luigi Sacco, Università di Milano, Ospedale L. Sacco, via G.B. Grassi 74, 20157 Milano, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Corsi
authors.forename: Luisa
authors.initials: L
authors.lastname: Fiandra
authors.forename: Clara
authors.initials: C
authors.lastname: De Palma
authors.forename: Miriam
authors.initials: M
authors.lastname: Colombo
authors.forename: Serena
authors.initials: S
authors.lastname: Mazzucchelli
authors.forename: Paolo
authors.initials: P
authors.lastname: Verderio
authors.forename: Raffaele
authors.initials: R
authors.lastname: Allevi
authors.forename: Antonella
authors.initials: A
authors.lastname: Tosoni
authors.forename: Manuela
authors.initials: M
authors.lastname: Nebuloni
authors.forename: Emilio
authors.initials: E
authors.lastname: Clementi
authors.forename: Davide
authors.initials: D
authors.lastname: Prosperi
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D001692:Biological Transport; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects*; D004738:Engineering; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D000068878:Trastuzumab; D023041:Xenograft Model Antitumor Assays
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab