title: Evaluation of the immunological profile of antibody-functionalized metal-filled single-walled carbon nanocapsules for targeted radiotherapy.
abstract: This study investigates the immune responses induced by metal-filled single-walled carbon nanotubes (SWCNT) under in vitro, ex vivo and in vivo settings. Either empty amino-functionalized CNTs [SWCNT-NH2(1)] or samarium chloride-filled amino-functionalized CNTs with [SmCl3@SWCNT-mAb (3)] or without [SmCl3@SWCNT-NH2(2)] Cetuximab functionalization were tested. Conjugates were added to RAW 264.7 or PBMC cells in a range of 1 μg/ml to 100 μg/ml for 24 h. Cell viability and IL-6/TNFα production were determined by flow cytometry and ELISA. Additionally, the effect of SWCNTs on the number of T lymphocytes, B lymphocytes and monocytes within the PBMC subpopulations was evaluated by immunostaining and flow cytometry. The effect on monocyte number in living mice was assessed after tail vein injection (150 μg of each conjugate per mouse) at 1, 7 and 13 days post-injection. Overall, our study showed that all the conjugates had no significant effect on cell viability of RAW 264.7 but conjugates 1 and 3 led to a slight increase in IL-6/TNFα. All the conjugates resulted in significant reduction in monocyte/macrophage cell numbers within PBMCs in a dose-dependent manner. Interestingly, monocyte depletion was not observed in vivo, suggesting their suitability for future testing in the field of targeted radiotherapy in mice.
authors.affiliation: University of Strasbourg, CNRS, Immunopathology and Therapeutic Chemistry, UPR 3572, 67000 Strasbourg, France.
authors.forename: Aritz
authors.initials: A
authors.lastname: Perez Ruiz de Garibay
authors.affiliation: University of Strasbourg, CNRS, Immunopathology and Therapeutic Chemistry, UPR 3572, 67000 Strasbourg, France.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Spinato
authors.affiliation: Institute of Pharmaceutical Science, Faculty of Life Sciences &Medicine, King's College London, London SE1 9NH, UK.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Klippstein
authors.affiliation: Institute of Pharmaceutical Science, Faculty of Life Sciences &Medicine, King's College London, London SE1 9NH, UK.
authors.forename: Maxime
authors.initials: M
authors.lastname: Bourgognon
authors.affiliation: Institut de Ciència de Materials de Barcelona (ICMAB-CSIC), Campus UAB, 08193, Bellaterra, Barcelona, Spain.
authors.forename: Markus
authors.initials: M
authors.lastname: Martincic
authors.affiliation: Catalan Institute of Nanoscience and Nanotechnology (ICN2), CSIC and The Barcelona Institute of Science and Technology, Campus UAB, Bellaterra, 08193 Barcelona, Spain.
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Pach
authors.affiliation: Catalan Institute of Nanoscience and Nanotechnology (ICN2), CSIC and The Barcelona Institute of Science and Technology, Campus UAB, Bellaterra, 08193 Barcelona, Spain.
authors.forename: Belén
authors.initials: B
authors.lastname: Ballesteros
authors.affiliation: University of Strasbourg, CNRS, Immunopathology and Therapeutic Chemistry, UPR 3572, 67000 Strasbourg, France.
authors.forename: Cécilia
authors.initials: C
authors.lastname: Ménard-Moyon
authors.affiliation: Institute of Pharmaceutical Science, Faculty of Life Sciences &Medicine, King's College London, London SE1 9NH, UK.
authors.forename: Khuloud T
authors.initials: KT
authors.lastname: Al-Jamal
authors.affiliation: Institut de Ciència de Materials de Barcelona (ICMAB-CSIC), Campus UAB, 08193, Bellaterra, Barcelona, Spain.
authors.forename: Gerard
authors.initials: G
authors.lastname: Tobias
authors.affiliation: University of Strasbourg, CNRS, Immunopathology and Therapeutic Chemistry, UPR 3572, 67000 Strasbourg, France.
authors.forename: Alberto
authors.initials: A
authors.lastname: Bianco
mesh_terms: D000818:Animals; D000906:Antibodies / Q000737:chemistry / Q000276:immunology; D002470:Cell Survival; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008262:Macrophage Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008670:Metals / Q000737:chemistry; D051379:Mice; D015394:Molecular Structure; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry / Q000648:ultrastructure; D037742:Nanotubes, Carbon / Q000737:chemistry / Q000648:ultrastructure; D000067996:RAW 264.7 Cells; D011878:Radiotherapy / Q000379:methods
chemical_list: D000906:Antibodies; D016207:Cytokines; D018836:Inflammation Mediators; D008670:Metals; D053769:Nanocapsules; D037742:Nanotubes, Carbon