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Open AccessArticle

Tumor Targeting by Monoclonal Antibody Functionalized Magnetic Nanoparticles

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Laboratory of Histology, Department of Health Sciences (DSS), Università del Piemonte Orientale “A. Avogadro”, Via Solaroli 17, 28100 Novara, Italy
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Laboratory of Pharmacology, Department of Health Sciences (DSS), Università del Piemonte Orientale “A. Avogadro”, Via Solaroli 17, 28100 Novara, Italy
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Department of Science and Technological Innovation (DISIT), Università del Piemonte Orientale “A. Avogadro”, Viale Teresa Michel 11, 15100 Alessandria, Italy
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Laboratory of Immunology, Department of Health Sciences (DSS), Università del Piemonte Orientale “A. Avogadro”, Via Solaroli 17, 28100 Novara, Italy
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Department of Applied Science and Technology (DISAT), Politecnico di Torino, Corso Duca degli Abruzzi 24, 10129 Torino, Italy
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Centro di Biotecnologie per la Ricerca Medica Applicata (BRMA), Via Solaroli 17, 28100 Novara, Italy
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Consorzio Interuniversitario per Biotecnologie (CIB), Località Padriciano 99, 34149 Area di Ricerca, TS, Italy
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Consorzio Interuniversitario Nazionale per la Scienza e Tecnologia dei Materiali (INSTM), 28100 Novara, Italy
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Present Address: Departamento de Microbiología, Facultad de Ciencias, Universidad de Granada, Campus Fuentenueva, s/n, 18071 Granada, Spain.
Nanomaterials 2019, 9(11), 1575; https://doi.org/10.3390/nano9111575
Received: 13 October 2019 / Revised: 31 October 2019 / Accepted: 4 November 2019 / Published: 6 November 2019
Tumor-targeted drug-loaded nanocarriers represent innovative and attractive tools for cancer therapy. Several magnetic nanoparticles (MNPs) were analyzed as potential tumor-targeted drug-loaded nanocarriers after functionalization with anti-Met oncogene (anti-Met/HGFR) monoclonal antibody (mAb) and doxorubicin (DOXO). Their cytocompatibility, stability, immunocompetence (immunoprecipitation), and their interactions with cancer cells in vitro (Perl’s staining, confocal microscopy, cytotoxic assays: MTT, real time toxicity) and with tumors in vivo (Perl’s staining) were evaluated. The simplest silica- and calcium-free mAb-loaded MNPs were the most cytocompatible, the most stable, and showed the best immunocompetence and specificity. These mAb-functionalized MNPs specifically interacted with the surface of Met/HGFR-positive cells, and not with Met/HGFR-negative cells; they were not internalized, but they discharged in the targeted cells DOXO, which reached the nucleus, exerting cytotoxicity. The presence of mAbs on DOXO-MNPs significantly increased their cytotoxicity on Met/HGFR-positive cells, while no such effect was detectable on Met/HGFR-negative cells. Bare MNPs were biocompatible in vivo; mAb presence on MNPs induced a better dispersion within the tumor mass when injected in situ in Met/HGFR-positive xenotumors in NOD/SCID-γnull mice. These MNPs may represent a new and promising carrier for in vivo targeted drug delivery, in which applied gradient and alternating magnetic fields can enhance targeting and induce hyperthermia respectively. View Full-Text
Keywords: magnetic nanoparticles; tumor targeting; monoclonal antibodies; cytotoxicity; doxorubicin magnetic nanoparticles; tumor targeting; monoclonal antibodies; cytotoxicity; doxorubicin
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MDPI and ACS Style

Oltolina, F.; Colangelo, D.; Miletto, I.; Clemente, N.; Miola, M.; Verné, E.; Prat, M.; Follenzi, A. Tumor Targeting by Monoclonal Antibody Functionalized Magnetic Nanoparticles. Nanomaterials 2019, 9, 1575.

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