Tumor Targeting by Monoclonal Antibody Functionalized Magnetic Nanoparticles
Metadata
Show full item recordAuthor
Oltolina, FrancescaEditorial
MDPI
Materia
Magnetic nanoparticles Tumor targeting Monoclonal antibodies Cytotoxicity Doxorubicin
Date
2019-11-06Referencia bibliográfica
Oltolina, F., Colangelo, D., Miletto, I., Clemente, N., Miola, M., Verné, E., ... & Follenzi, A. (2019). Tumor Targeting by Monoclonal Antibody Functionalized Magnetic Nanoparticles. Nanomaterials, 9(11), 1575.
Sponsorship
This research was funded by AIRC—Italy, grant number IG n. 13166, Compagnia di San Paolo, grant CSP-Torino-Piemonte: 12-CSP-C04-018, and the Università del Piemonte Orientale “A. Avogadro”, grant 021Abstract
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-y
null 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.