Abstract
Chemical vapor deposition (CVD) methods to create carbon nanotubes (CNTs) with specific dopant atoms have been of interest in biomedical applications due to the relative ease of synthesis of doped CNTs with controlled physical properties. However, CNTs generated from CVD are often heterogeneous in chemical functionality, size, aspect ratio, number of walls, and conducting properties resulting in potential inconsistencies during measurement of the physiological activity of cell-CNT interactions. In this work, the biocompatibility of nitrogen-doped multiwalled carbon nanotubes (CNx) with both murine fibroblasts and human hematopoietic stem cells (hHSC) was evaluated. CNx were synthesized by CVD, purified, characterized, and classified into three fractions designated as small-CNx (S-CNx), medium (M-CNx), and large (L-CNx). Mammalian cells were incubated with CNx doses between 0.07 and 70 μg/mL, and cell viability was evaluated. hHSC and murine fibroblast both demonstrated non-significant differences in proliferation rates when exposed to M-CN, whereas, either cells experienced inhibited growth following exposure to either S-CNx and L-CNx under the same conditions. In this work, it has been demonstrated that CNTs produced by CVD have differences on the biocompatibility with mammalian cells, but the M-CNx could be a great candidate for biomedical applications.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Andrade-Zaldívar H, Kalixto-Sánchez MA, de la Rosa APB, De León-Rodríguez A (2011) Expansion of human hematopoietic cells from umbilical cord blood using roller bottles in CO2 and CO2-free atmosphere. Stem Cells Dev 20:593–598. https://doi.org/10.1089/scd.2010.0236
Bari S et al (2013) Protective role of functionalized single walled carbon nanotubes enhance ex vivo expansion of hematopoietic stem and progenitor cells in human umbilical cord blood nanomedicine. Nanotechnol Biol Med 9:1304–1316. https://doi.org/10.1016/j.nano.2013.05.009
Bari S et al (2015) Mitochondrial superoxide reduction and cytokine secretion skewing by carbon nanotube scaffolds enhance ex vivo expansion of human cord blood hematopoietic progenitors nanomedicine. Nanotechnol Biol Med 11:1643–1656. https://doi.org/10.1016/j.nano.2015.06.005
Bazargan A, McKay G (2012) A review – Synthesis of carbon nanotubes from plastic wastes. Chem Eng J 195-196:377–391. https://doi.org/10.1016/j.cej.2012.03.077
Blazer-Yost BL et al (2011) Effect of carbon nanoparticles on renal epithelial cell structure, barrier function, and protein expression. Nanotoxicology 5:354–371. https://doi.org/10.3109/17435390.2010.514076
Canapè C, Foillard S, Bonafè R, Maiocchi A, Doris E (2015) Comparative assessment of the in vitro toxicity of some functionalized carbon nanotubes and fullerenes. RSC Adv 5:68446–68453. https://doi.org/10.1039/c5ra11489f
Canavan HE, Cheng X, Graham DJ, Ratner BD, Castner DG (2005) Cell sheet detachment affects the extracellular matrix: a surface science study comparing thermal liftoff, enzymatic, and mechanical methods. J Biomed Mater Res Part A 75A:1–13. https://doi.org/10.1002/jbm.a.30297
Carrero-Sanchez JC, Elias AL, Mancilla R, Arrellin G, Terrones H, Laclette JP, Terrones M (2006) Biocompatibility and toxicological studies of carbon nanotubes doped with nitrogen. Nano Lett 6:1609–1616. https://doi.org/10.1021/nl060548p
Cui HF, Vashist SK, Al-Rubeaan K, Luong JH, Sheu FS (2010) Interfacing carbon nanotubes with living mammalian cells and cytotoxicity issues. Chem Res Toxicol 23:1131–1147. https://doi.org/10.1021/tx100050h
Cui X, Wan B, Yang Y, Ren X, Guo LH (2017) Length effects on the dynamic process of cellular uptake and exocytosis of single-walled carbon nanotubes in murine macrophage cells. Sci Rep 7:1518. https://doi.org/10.1038/s41598-017-01746-9
De Volder MF, Tawfick SH, Baughman RH, Hart AJ (2013) Carbon nanotubes: present and future commercial applications. Science 339:535–539. https://doi.org/10.1126/science.1222453
Escobar Barrios VA, Rangel Méndez JR, Pérez Aguilar NV, Andrade Espinosa G, Dávila Rodríguez JL (2012) FTIR - an essential characterization technique for polymeric materials. In: Theophanides T (ed) Infrared Spectroscopy. IntechOpen. https://doi.org/10.5772/36044
Ferreira L, Karp JM, Nobre L, Langer R (2008) New opportunities: the use of nanotechnologies to manipulate and track stem cells. Cell Stem Cell 3:136–146. https://doi.org/10.1016/j.stem.2008.07.020
Fisher C, Rider AE, Jun Han Z, Kumar S, Levchenko I, Ostrikov K (2012) Applications and nanotoxicity of carbon nanotubes and graphene in biomedicine. J Nanomater 2012:1–19. https://doi.org/10.1155/2012/315185
He S et al (2017) Biocompatible carbon nanotube fibers for implantable supercapacitors. Carbon 122:162–167. https://doi.org/10.1016/j.carbon.2017.06.053
Hirata E, Akasaka T, Uo M, Takita H, Watari F, Yokoyama A (2012) Carbon nanotube-coating accelerated cell adhesion and proliferation on poly (L-lactide). Appl Surf Sci 262:24–27. https://doi.org/10.1016/j.apsusc.2012.01.012
Huang L, Liu M, Huang H, Wen Y, Zhang X, Wei Y (2018) Recent advances and progress on melanin-like materials and their biomedical applications. Biomacromolecules 19:1858–1868. https://doi.org/10.1021/acs.biomac.8b00437
Jiang K, Eitan A, Schadler LS, Ajayan PM, Siegel RW, Grobert N, Mayne M, Reyes-Reyes M, Terrones H, Terrones M (2003) Selective attachment of gold nanoparticles to nitrogen-doped carbon nanotubes. Nano Lett 3:275–277. https://doi.org/10.1021/nl025914t
Jourdain V, Bichara C (2013) Current understanding of the growth of carbon nanotubes in catalytic chemical vapour deposition. Carbon 58:2–39. https://doi.org/10.1016/j.carbon.2013.02.046
Kaiser JP, Buerki-Thurnherr T, Wick P (2013) Influence of single walled carbon nanotubes at subtoxical concentrations on cell adhesion and other cell parameters of human epithelial cells Journal of King Saud University. Science 25:15–27. https://doi.org/10.1016/j.jksus.2012.06.003
Kamalakaran R et al (2000) Synthesis of thick and crystalline nanotube arrays by spray pyrolysis. Appl Phys Lett 77:3385–3387
Kim AD, Stachura DL, Traver D (2014) Cell signaling pathways involved in hematopoietic stem cell specification. Exp Cell Res 329:227–233. https://doi.org/10.1016/j.yexcr.2014.10.011
Krenning G, Zeisberg EM, Kalluri R (2010) The origin of fibroblasts and mechanism of cardiac fibrosis. J Cell Physiol 225:631–637. https://doi.org/10.1002/jcp.22322
Kunzmann A, Andersson B, Thurnherr T, Krug H, Scheynius A, Fadeel B (2011) Toxicology of engineered nanomaterials: focus on biocompatibility, biodistribution and biodegradation. Biochimica et Biophysica Acta (BBA) - general subjects 1810:361–373. https://doi.org/10.1016/j.bbagen.2010.04.007
Lanone S, Andujar P, Kermanizadeh A, Boczkowski J (2013) Determinants of carbon nanotube toxicity. Adv drug Deliv Rev. https://doi.org/10.1016/j.addr.2013.07.019
Li DJ, Niu LF (2003) Influence of N atomic percentages on cell attachment for CNx coatings. Bull Mater Sci 26:371–375. https://doi.org/10.1007/BF02711178
Li L, Lin R, He H, Sun M, Jiang L, Gao M (2014) Interaction of amidated single-walled carbon nanotubes with protein by multiple spectroscopic methods. J Lumin 145:125–131. https://doi.org/10.1016/j.jlumin.2013.07.008
Liao L, Pan C (2011) Enhanced electrochemical capacitance of nitrogen-doped carbon nanotubes synthesized from amine flames soft. Nanoscience Lett 01:16–23. https://doi.org/10.4236/snl.2011.11004
Lim WF, Inoue-Yokoo T, Tan KS, Lai MI, Sugiyama D (2013) Hematopoietic cell differentiation from embryonic and induced pluripotent stem cell. Stem Cell Res Ther 4:71
Liu Y, Zhao Y, Sun B, Chen C (2013) Understanding the toxicity of carbon nanotubes. Acc Chem Res 46:702–713. doi.org/10.1021/ar300028m
Liu Z et al (2014) Carboxylation of multiwalled carbon nanotube enhanced its biocompatibility with L02 cells through decreased activation of mitochondrial apoptotic pathway. J Biomed Mater Res Part A 102:665–673. https://doi.org/10.1002/jbm.a.34729
Liu M et al (2015) Self-polymerization of dopamine and polyethyleneimine: novel fluorescent organic nanoprobes for biological imaging applications. J Mater Chem B 3:3476–3482. https://doi.org/10.1039/c4tb02067g
Liu M, Zeng G, Wang K, Wan Q, Tao L, Zhang X, Wei Y (2016a) Recent developments in polydopamine: an emerging soft matter for surface modification and biomedical applications. Nanoscale 8:16819–16840. https://doi.org/10.1039/c5nr09078d
Liu Z, Liu Y, Peng D (2016b) Hydroxylation of multi-walled carbon nanotubes: enhanced biocompatibility through reduction of oxidative stress initiated cell membrane damage, cell cycle arrestment and extrinsic apoptotic pathway. Environ Toxicol Pharmacol 47:124–130. https://doi.org/10.1016/j.etap.2016.09.013
Matsuoka M, Akasaka T, Totsuka Y, Watari F (2010) Strong adhesion of Saos-2 cells to multi-walled carbon nanotubes. Mater Sci Eng: B 173:182–186. https://doi.org/10.1016/j.mseb.2009.12.044
McAnulty RJ (2007) Fibroblasts and myofibroblasts: their source, function and role in disease. Int J Biochem Cell Biol 39:666–671. https://doi.org/10.1016/j.biocel.2006.11.005
Meng J, Song L, Xu H, Kong H, Wang C, Guo X, Xie S (2005) Effects of single-walled carbon nanotubes on the functions of plasma proteins and potentials in vascular prostheses. Nanomed : Nanotechnol Biol Med 1:136–142. https://doi.org/10.1016/j.nano.2005.03.003
Meysami SS, Dillon F, Koós AA, Aslam Z, Grobert N (2013a) Aerosol-assisted chemical vapour deposition synthesis of multi-wall carbon nanotubes: I mapping the reactor. Carbon 58:151–158. https://doi.org/10.1016/j.carbon.2013.02.044
Meysami SS, Koós AA, Dillon F, Grobert N (2013b) Aerosol-assisted chemical vapour deposition synthesis of multi-wall carbon nanotubes: II an analytical study. Carbon 58:159–169. https://doi.org/10.1016/j.carbon.2013.02.041
Mihalchik AL et al (2015) Effects of nitrogen-doped multi-walled carbon nanotubes compared to pristine multi-walled carbon nanotubes on human small airway epithelial cells. Toxicology. https://doi.org/10.1016/j.tox.2015.03.008
Mubarak NM, Abdullah EC, Jayakumar NS, Sahu JN (2014) An overview on methods for the production of carbon nanotubes. J Ind Eng Chem 20:1186–1197. https://doi.org/10.1016/j.jiec.2013.09.001
Mundra RV, Wu X, Sauer J, Dordick JS, Kane RS (2014) Nanotubes in biological applications. Curr Opin Biotechnol 28:25–32. https://doi.org/10.1016/j.copbio.2013.10.012
Munguía-Lopez JG, Muñoz-Sandoval E, Ortiz-Medina J, Rodriguez-Macias FJ, De Leon-Rodriguez A (2015) Effects of nitrogen-doped multiwall carbon nanotubes on murine fibroblasts. J Nanomater 2015:1–7. https://doi.org/10.1155/2015/801606
Muñoz-Sandoval E, Fajardo-Díaz JL, Sánchez-Salas R, Cortés-López AJ, López-Urías F (2018) Two sprayer CVD synthesis of nitrogen-doped carbon sponge-type nanomaterials. Sci Rep 8:2983. https://doi.org/10.1038/s41598-018-20079-9
Nxumalo EN, Nyamori VO, Coville NJ (2008) CVD synthesis of nitrogen doped carbon nanotubes using ferrocene/aniline mixtures. J Organomet Chem 693:2942–2948. https://doi.org/10.1016/j.jorganchem.2008.06.015
Pulskamp K, Diabate S, Krug HF (2007) Carbon nanotubes show no sign of acute toxicity but induce intracellular reactive oxygen species in dependence on contaminants. Toxicol Lett 168:58–74. https://doi.org/10.1016/j.toxlet.2006.11.001
Ryabenko AG, Dorofeeva TV, Zvereva GI (2004) UV–VIS–NIR spectroscopy study of sensitivity of single-wall carbon nanotubes to chemical processing and Van-der-Waals SWNT/SWNT interaction. Verification of the SWNT content measurements by absorption. Spectrosc Carbon 42:1523–1535. https://doi.org/10.1016/j.carbon.2004.02.005
Ryoo SR, Kim YK, Kim MH, Min DH (2010) Behaviors of NIH-3T3 fibroblasts on graphene/carbon nanotubes: proliferation, focal adhesion, and gene transfection studies. ACS Nano 4:6587–6598. https://doi.org/10.1021/nn1018279
Sabuncu AC, Kalluri BS, Qian S, Stacey MW, Beskok A (2010) Dispersion state and toxicity of mwCNTs in cell culture medium with different T80 concentrations. Colloids Surf B: Biointerfaces 78:36–43. https://doi.org/10.1016/j.colsurfb.2010.02.005
Sanchez-Salas R (2015) Sintesis de nanotubos de carbono dopados con nitrogeno: un estudio sistemático. Instituto Potosino de Investigación Científica y Tecnológica, A.C (IPICyT)
Shah KA, Tali BA (2016) Synthesis of carbon nanotubes by catalytic chemical vapour deposition: a review on carbon sources, catalysts and substrates. Mater Sci Semicond Process 41:67–82. https://doi.org/10.1016/j.mssp.2015.08.013
Shi Y et al (2017) Biomimetic PEGylation of carbon nanotubes through surface-initiated RAFT polymerization. Mater Sci Eng C Mater Biol Appl 80:404–410. https://doi.org/10.1016/j.msec.2017.06.009
Sohaebuddin SK, Thevenot PT, Baker D, Eaton JW, Tang L (2010) Nanomaterial cytotoxicity is composition, size, and cell type dependent. Part Fibre Toxicol 7:22. https://doi.org/10.1186/1743-8977-7-22
Tucureanu V, Matei A, Avram AM (2016) FTIR Spectroscopy for Carbon Family Study. Crit Rev Anal Chem 46:502–520. https://doi.org/10.1080/10408347.2016.1157013
Weissleder R (2001) A clearer vision for in vivo imaging. Nat Biotechnol 19:316–317. https://doi.org/10.1038/86684
Wu X, Tao Y, Lu Y, Dong L, Hu Z (2006) High-pressure pyrolysis of melamine route to nitrogen-doped conical hollow and bamboo-like carbon nanotubes. Diam Relat Mater 15:164–170. https://doi.org/10.1016/j.diamond.2005.09.018
Xiao H et al (2012) Photodynamic effects of chlorin e6 attached to single wall carbon nanotubes through noncovalent interactions. Carbon 50:1681–1689. https://doi.org/10.1016/j.carbon.2011.12.013
Zhang X et al (2010) Biodistribution and toxicity of nanodiamonds in mice after intratracheal instillation. Toxicol Lett 198:237–243. https://doi.org/10.1016/j.toxlet.2010.07.001
Zhang X et al (2011a) Distribution and biocompatibility studies of graphene oxide in mice after intravenous administration. Carbon 49:986–995. https://doi.org/10.1016/j.carbon.2010.11.005
Zhang X, Zhu Y, Li J, Zhu Z, Li J, Li W, Huang Q (2011b) Tuning the cellular uptake and cytotoxicity of carbon nanotubes by surface hydroxylation. J Nanopart Res 13:6941–6952. https://doi.org/10.1007/s11051-011-0603-9
Zhang M, Zhou X, Iijima S, Yudasaka M (2012a) Small-sized carbon nanohorns enabling cellular uptake control. Small 8:2524–2531. https://doi.org/10.1002/smll.201102595
Zhang X, Hu W, Li J, Tao L, Wei Y (2012b) A comparative study of cellular uptake and cytotoxicity of multi-walled carbon nanotubes, graphene oxide, and nanodiamond. Toxicol Res 1:1. https://doi.org/10.1039/c2tx20006f
Zhang X et al (2012c) Biocompatible polydopamine fluorescent organic nanoparticles: facile preparation and cell imaging. Nanoscale 4:5581–5584. https://doi.org/10.1039/c2nr31281f
Zhang X et al (2015) Interaction of tannic acid with carbon nanotubes: enhancement of dispersibility and biocompatibility. Toxicol Res 4:160–168. https://doi.org/10.1039/c4tx00066h
Zhang X, Huang Q, Deng F, Huang H, Wan Q, Liu M, Wei Y (2017) Mussel-inspired fabrication of functional materials and their environmental applications: Progress and prospects. Appl Mater Today 7:222–238. https://doi.org/10.1016/j.apmt.2017.04.001
Zhang M et al (2018) Size-dependent cell uptake of carbon nanotubes by macrophages: a comparative and quantitative study. Carbon 127:93–101. https://doi.org/10.1016/j.carbon.2017.10.085
Zhao X, Liu R (2012) Recent progress and perspectives on the toxicity of carbon nanotubes at organism, organ, cell, and biomacromolecule levels. Environ Int 40:244–255. https://doi.org/10.1016/j.envint.2011.12.003
Zhao F, Zhao Y, Liu Y, Chang X, Chen C, Zhao Y (2011a) Cellular uptake, intracellular trafficking, and cytotoxicity of nanomaterials. Small 7:1322–1337. https://doi.org/10.1002/smll.201100001
Zhao ML, Li DJ, Yuan L, Yue YC, Liu H, Sun X (2011b) Differences in cytocompatibility and hemocompatibility between carbon nanotubes and nitrogen-doped carbon nanotubes. Carbon 49:3125–3133. https://doi.org/10.1016/j.carbon.2011.03.037
Zhou L, Forman HJ, Ge Y, Lunec J (2017) Multi-walled carbon nanotubes: a cytotoxicity study in relation to functionalization, dose and dispersion. Toxicol in vitro 42:292–298. https://doi.org/10.1016/j.tiv.2017.04.027
Zhu Y, Li W, Li Q, Li Y, Li Y, Zhang X, Huang Q (2009) Effects of serum proteins on intracellular uptake and cytotoxicity of carbon nanoparticles. Carbon 47:1351–1358. https://doi.org/10.1016/j.carbon.2009.01.026
Acknowledgments
The authors thank L. Aldana and Abdullah Chaudhary for the English review and V. Balderas for his technical assistance.
Funding
This research was funded by The Marcos Moshinsky Foundation and CONACYT-Mexico grant number CB-2013-220744 and 250279.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic supplementary material
ESM 1
(DOCX 293 kb)
Rights and permissions
About this article
Cite this article
Munguia-Lopez, J.G., Juarez, R., Muñoz-Sandoval, E. et al. Biocompatibility of nitrogen-doped multiwalled carbon nanotubes with murine fibroblasts and human hematopoietic stem cells. J Nanopart Res 21, 193 (2019). https://doi.org/10.1007/s11051-019-4637-8
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s11051-019-4637-8