期刊
ADVANCED FUNCTIONAL MATERIALS
卷 23, 期 25, 页码 3173-3184出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adfm.201202898
关键词
magnetic carbon nanotubes; biomolecular recognition; cell sorting; magnetic fluid hyperthermia; molecular dynamics
类别
资金
- EU [ITN FINELUMEN PITN-GA-2008-215399]
- FRS-FNRS, (FRFC) [2.4.550.09, 2.4.617.07.F]
- FRS-FNRS, (MIS) [F.4.505.10.F]
- Loterie Nationale
- Region Wallonne through the TARGAN project
- TINTIN ARC project [09/14-023]
- University of Namur
- FRS-FNRS
- IAP INANOMAT
- FNRS [FRFC 2.4508.08, IISN 4.4507.10]
With the aim to design addressable magnetically-active carbon nanotubes (CNTs) for cancer treatment, the use of Fe-filled CNTs (Fe@MWCNTs) as multifunctional scaffolds is reported for exohedrally anchoring a monoclonal antibody (mAb) known to bind a plasma membrane receptor over-expressed in several cancer cells (EGFR). Comprehensive microscopic (transmission electron microscopy, atomic force microscopy, and scanning electron microscopy) and spectroscopic (Raman, Fe-57 Mossbauer, energy dispersive spectroscopy, X-ray photoelectron spectroscopy (XPS), X-ray diffraction) characterizations reveal the efficient confinement of magnetically-active Fe phases (-Fe and Fe3C), while compositional evaluations through XPS, thermogravimetric analysis and gel electrophoresis confirm that mAb immobilization onto Fe@MWCNTs occurs. Enzyme-linked immunosorbent assay (ELISA), confocal microscopy imaging and western blotting confirm the targeting action toward EGFR-overexpressing cell lines (EGFR+). In vitro magnetic filtration experiments demonstrate that a selective removal of EGFR+ cells from a mixed population of healthy cell lines could be obtained in very short times (approximate to 10 min). Cytotoxicity evaluations by classic cell staining procedures after application of an electromagnetic radiation inducing magnetic fluid hyperthermia (MFH), show a selective suppression of the EGFR+ cell line. Molecular dynamics and docking simulations of the hybrid mAb/Fe@MWCNTs conjugates nicely show how the presence of the CNT framework does not sterically affect the conformational properties of the two antigen binding regions, further supporting the biochemical findings.
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