Antonella Rocca1, Attilio Marino2, Serena Del Turco3, Valentina Cappello4, Paola Parlanti5, Mario Pellegrino6, Dmitri Golberg7, Virgilio Mattoli8, Gianni Ciofani9. 1. Scuola Superiore Sant'Anna, The BioRobotics Institute, Viale Rinaldo Piaggio 34, 56025 Pontedera (Pisa), Italy; Istituto Italiano di Tecnologia, Center for Micro-BioRobotics @SSSA, Viale Rinaldo Piaggio 34, 56025 Pontedera (Pisa), Italy. Electronic address: a.rocca@sssup.it. 2. Scuola Superiore Sant'Anna, The BioRobotics Institute, Viale Rinaldo Piaggio 34, 56025 Pontedera (Pisa), Italy; Istituto Italiano di Tecnologia, Center for Micro-BioRobotics @SSSA, Viale Rinaldo Piaggio 34, 56025 Pontedera (Pisa), Italy. 3. CNR, Institute of Clinical Physiology, Via Moruzzi 1, 56124 Pisa, Italy. 4. Istituto Italiano di Tecnologia, Center for Nanotechnology Innovation @NEST, Piazza San Silvestro 12, 56127 Pisa, Italy. 5. Istituto Italiano di Tecnologia, Center for Nanotechnology Innovation @NEST, Piazza San Silvestro 12, 56127 Pisa, Italy; NEST, Scuola Normale Superiore and Istituto di Nanoscienze-CNR, Piazza San Silvestro 12, 56127 Pisa, Italy. 6. University of Pisa, Dipartimento di Ricerca Traslazionale e delle Nuove Tecnologie in Medicina e Chirurgia, Via S. Zeno 31, 56126 Pisa, Italy. 7. National Institute for Materials Science (NIMS), International Center for Materials Nanoarchitectonics (MANA), Namiki 1-1, 305-0044 Tsukuba (Ibaraki), Japan. 8. Istituto Italiano di Tecnologia, Center for Micro-BioRobotics @SSSA, Viale Rinaldo Piaggio 34, 56025 Pontedera (Pisa), Italy. 9. Istituto Italiano di Tecnologia, Center for Micro-BioRobotics @SSSA, Viale Rinaldo Piaggio 34, 56025 Pontedera (Pisa), Italy; Politecnico di Torino, Department of Mechanical and Aerospace Engineering, Corso Duca degli Abruzzi 24, 10129 Torino, Italy. Electronic address: gianni.ciofani@polito.it.
Abstract
BACKGROUND: Boron nitride nanotubes (BNNTs) represent a new opportunity for drug delivery and clinical therapy. The present work has the objective to investigate pectin-coated BNNTs (P-BNNTs) for their biocompatibility on macrophage cultures, since these cells are among the first components of the immune system to interact with administered nanoparticles. METHODS: As first step, the potential toxicity of P-BNNTs is verified in terms of proliferation, oxidative stress induction and apoptosis/necrosis phenomena. Thereafter, the modulation of immune cell response following P-BNNT exposure is evaluated at gene and protein level, in particular focusing on cytokine release. Finally, P-BNNT internalization is assessed through transmission electron microscopy and confocal microscopy. RESULTS: The results proved that P-BNNTs are not toxic for macrophages up to 50 μg/ml after 24 h of incubation. The cytokine expression is not affected by P-BNNT administration both at gene and protein level. Moreover, P-BNNTs are internalized by macrophages without impairments of the cell structures. CONCLUSIONS: Collected data suggest that P-BNNTs cause neither adverse effects nor inflammation processes in macrophages. GENERAL SIGNIFICANCE: These findings represent the first and fundamental step in immune compatibility evaluation of BNNTs, mandatory before any further pre-clinical testing.
BACKGROUND:Boron nitride nanotubes (BNNTs) represent a new opportunity for drug delivery and clinical therapy. The present work has the objective to investigate pectin-coated BNNTs (P-BNNTs) for their biocompatibility on macrophage cultures, since these cells are among the first components of the immune system to interact with administered nanoparticles. METHODS: As first step, the potential toxicity of P-BNNTs is verified in terms of proliferation, oxidative stress induction and apoptosis/necrosis phenomena. Thereafter, the modulation of immune cell response following P-BNNT exposure is evaluated at gene and protein level, in particular focusing on cytokine release. Finally, P-BNNT internalization is assessed through transmission electron microscopy and confocal microscopy. RESULTS: The results proved that P-BNNTs are not toxic for macrophages up to 50 μg/ml after 24 h of incubation. The cytokine expression is not affected by P-BNNT administration both at gene and protein level. Moreover, P-BNNTs are internalized by macrophages without impairments of the cell structures. CONCLUSIONS: Collected data suggest that P-BNNTs cause neither adverse effects nor inflammation processes in macrophages. GENERAL SIGNIFICANCE: These findings represent the first and fundamental step in immune compatibility evaluation of BNNTs, mandatory before any further pre-clinical testing.
Authors: Ashleigh D Smith McWilliams; Carlos A de Los Reyes; Lucy Liberman; Selin Ergülen; Yeshayahu Talmon; Matteo Pasquali; Angel A Martí Journal: Nanoscale Adv Date: 2018-12-17