Functionalized Fe-filled multiwalled carbon nanotubes as multifunctional scaffolds for magnetization of cancer cells

R. Marega, F. De Leo, F. Pineux, J. Sgrignani, A. Magistrato, A.D. Naik, Y. Garcia, L. Flamant, C. Michiels, D. Bonifazi

Résultats de recherche: Contribution à un journal/une revueArticle

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Résumé

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 Mossbauer, energy dispersive spectroscopy, X-ray photoelectron spectroscopy (XPS), X-ray diffraction) characterizations reveal the efficient confinement of magnetically-active Fe phases (α-Fe and FeC), 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 (≈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. Encapsulation of Fe phases inside multiwalled carbon nanotubes (MWCNTs) allows isolating reactive magnetic phases exerting magnetic fluid hyperthermia responses. In particular, bioconjugation of Fe@MWCNTs with monoclonal antibody Cetuximab enables the selective in vitro cancer cell sorting and stimuli-induced cytotoxicity under application of external magnetic inputs. Molecular dynamics calculations shed further light on binding modes and conformational properties of the Ab moieties linked on to the tubular carbon framework.
langue originaleAnglais
Pages (de - à)3173-3184
Nombre de pages12
journalAdvanced functional materials
Volume23
Numéro de publication25
Les DOIs
étatPublié - 2013

Empreinte digitale

Multiwalled carbon nanotubes (MWCN)
Scaffolds
Monoclonal antibodies
Magnetization
Cells
Carbon Nanotubes
Monoclonal Antibodies
Carbon nanotubes
Magnetic fluids
Cytotoxicity
Molecular dynamics
X ray photoelectron spectroscopy
Immunosorbents
Oncology
Confocal microscopy
Cell membranes
Antigens
Electrophoresis
Encapsulation
Sorting

Citer ceci

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title = "Functionalized Fe-filled multiwalled carbon nanotubes as multifunctional scaffolds for magnetization of cancer cells",
abstract = "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 Mossbauer, energy dispersive spectroscopy, X-ray photoelectron spectroscopy (XPS), X-ray diffraction) characterizations reveal the efficient confinement of magnetically-active Fe phases (α-Fe and FeC), 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 (≈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. Encapsulation of Fe phases inside multiwalled carbon nanotubes (MWCNTs) allows isolating reactive magnetic phases exerting magnetic fluid hyperthermia responses. In particular, bioconjugation of Fe@MWCNTs with monoclonal antibody Cetuximab enables the selective in vitro cancer cell sorting and stimuli-induced cytotoxicity under application of external magnetic inputs. Molecular dynamics calculations shed further light on binding modes and conformational properties of the Ab moieties linked on to the tubular carbon framework.",
author = "R. Marega and {De Leo}, F. and F. Pineux and J. Sgrignani and A. Magistrato and A.D. Naik and Y. Garcia and L. Flamant and C. Michiels and D. Bonifazi",
year = "2013",
doi = "10.1002/adfm.201202898",
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pages = "3173--3184",
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Functionalized Fe-filled multiwalled carbon nanotubes as multifunctional scaffolds for magnetization of cancer cells. / Marega, R.; De Leo, F.; Pineux, F.; Sgrignani, J.; Magistrato, A.; Naik, A.D.; Garcia, Y.; Flamant, L.; Michiels, C.; Bonifazi, D.

Dans: Advanced functional materials, Vol 23, Numéro 25, 2013, p. 3173-3184.

Résultats de recherche: Contribution à un journal/une revueArticle

TY - JOUR

T1 - Functionalized Fe-filled multiwalled carbon nanotubes as multifunctional scaffolds for magnetization of cancer cells

AU - Marega, R.

AU - De Leo, F.

AU - Pineux, F.

AU - Sgrignani, J.

AU - Magistrato, A.

AU - Naik, A.D.

AU - Garcia, Y.

AU - Flamant, L.

AU - Michiels, C.

AU - Bonifazi, D.

PY - 2013

Y1 - 2013

N2 - 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 Mossbauer, energy dispersive spectroscopy, X-ray photoelectron spectroscopy (XPS), X-ray diffraction) characterizations reveal the efficient confinement of magnetically-active Fe phases (α-Fe and FeC), 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 (≈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. Encapsulation of Fe phases inside multiwalled carbon nanotubes (MWCNTs) allows isolating reactive magnetic phases exerting magnetic fluid hyperthermia responses. In particular, bioconjugation of Fe@MWCNTs with monoclonal antibody Cetuximab enables the selective in vitro cancer cell sorting and stimuli-induced cytotoxicity under application of external magnetic inputs. Molecular dynamics calculations shed further light on binding modes and conformational properties of the Ab moieties linked on to the tubular carbon framework.

AB - 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 Mossbauer, energy dispersive spectroscopy, X-ray photoelectron spectroscopy (XPS), X-ray diffraction) characterizations reveal the efficient confinement of magnetically-active Fe phases (α-Fe and FeC), 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 (≈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. Encapsulation of Fe phases inside multiwalled carbon nanotubes (MWCNTs) allows isolating reactive magnetic phases exerting magnetic fluid hyperthermia responses. In particular, bioconjugation of Fe@MWCNTs with monoclonal antibody Cetuximab enables the selective in vitro cancer cell sorting and stimuli-induced cytotoxicity under application of external magnetic inputs. Molecular dynamics calculations shed further light on binding modes and conformational properties of the Ab moieties linked on to the tubular carbon framework.

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