Toxicity of Carbon Nanotubes as Anti-Tumor Drug Carriers

Figures & data

Figure 1 Schematic diagram illustrating the cells entering process of anti-tumor nanometer preparation with CNTs as a carrier.

Figure 2 This figure shows the sites that CNTs may accumulate after separation from anticancer drugs, resulting in toxicity to different organs. CNTs mainly cause damage and toxicity to organs such as heart, liver, lung, kidney, brain and embryo.

Table 1 Toxicities of CNTs to Different Organs

Carbon Nanotubes	Subject	Types of Toxicity	Result	Reference
MWCNTs	Male Sprague Dawley rats	Nervous system	Inhalation of MWCNTs significantly alters the balance between sympathetic and parasympathetic nervous system.	[^Citation130]
MWCNTs	Mice	Nervous System and BBB	Acute pulmonary exposure to MWCNTs induce nerve inflammation responses dependent on the disruption of BBB integrity.	[^Citation131]
CNTs	Male NMRI mice	Neurotoxicity	CNTs may cause behavioral toxicity associated with depression or anxiety expression.	[^Citation132]
SWCNTs	PC-12 cells	Neurotoxicity	SWCNTs are toxic to PC-12 cells and more toxic to differentiated PC-12 cells.	[^Citation133]
SWCNTs	Male C57BL/6 mice	Pulmonary immune system	SWCNTs can increase susceptibility to respiratory viral infections as a novel mechanism of toxicity.	[^Citation134]
SWCNTs	Six-week-old specific-pathogen-free ICR mice	Immune toxicity and reproductive toxicity	SWCNTs produce immune toxicity and have an impact on reproduction and development.	[^Citation135]
SWCNTs	BALB/c macrophage cell line J774A and Female BALB/c mice	Immune toxicity	SWCNTs are immune toxic to the body, and the dispersion of SWCNTs is negatively correlated with immune toxicity.	[^Citation136]
MWCNTs	T lymphocytes	Immune toxicity	MWCNTs are toxic to human T cells in a concentration-dependent manner.	[^Citation137]
SWCNTs	Six to eight weeks old females of the CD1 outbred strain. Mouse ES cell line D3 and NIH3T3 cells	Embryo toxicity	SWCNTs can trigger embryo toxicity in mammals.	[^Citation138]
CNTs	Kunming mice	Embryo toxicity	CNTs can cause embryo toxicity, damage to the fetus and even miscarriage.	[^Citation139]
MWCNTs	Zebrafish embryo	Embryo toxicity	MWCNTs have serious developmental toxicity, which is related to the length of MWCNTs.	[^Citation140]
CNTs	Mouse embryonic fibroblasts (MEFs) and p53+/− (C57BL/6J) male and female mice	Embryo toxicity	CNTs may induce embryo toxicity, which is hereditary.	[^Citation141]
Oxidized SWCNTs	Artemia salina	Developmental toxicity	O-SWCNTs cause deformity to salina and produce a lot of ROS.	[^Citation142]
CNTs	Male BALB/c mice	Genital toxicity	CNTs have toxic effects on the reproductive organs of mice.	[^Citation143]
SWCNTs and MWCNTs	MeT-5A cells and BEAS 2B cells	Genotoxicity	MWCNTs and SWCNTs induce DNA damage in MeT-5A cells.	[^Citation144]

Zheng W, McKinney W, Kashon M, et al. The influence of inhaled multi-walled carbon nanotubes on the autonomic nervous system. Part Fibre Toxicol. 2016;13:8. doi:10.1186/s12989-016-0119-726864021

 PubMed Web of Science ®Google Scholar

Aragon MJ, Topper L, Tyler CR, et al. Serum-borne bioactivity caused by pulmonary multiwalled carbon nanotubes induces neuroinflammation via blood-brain barrier impairment. Proc Natl Acad Sci U S A. 2017;114:E1968–E1976. doi:10.1073/pnas.161607011428223486

 PubMed Web of Science ®Google Scholar

Gholamine B, Karimi I, Salimi A, et al. Neurobehavioral toxicity of carbon nanotubes in mice. Toxicol Ind Health. 2017;33:340–350. doi:10.1177/074823371664438127230352

 PubMedGoogle Scholar

Larner SF, Wang J, Goodman J, et al. In vitro neurotoxicity resulting from exposure of cultured neural cells to several types of nanoparticles. J Cell Death. 2017;10:1179670717694523. doi:10.1177/117967071769452328469474

 PubMedGoogle Scholar

Chen H, Zheng X, Nicholas J, et al. Single-walled carbon nanotubes modulate pulmonary immune responses and increase pandemic influenza a virus titers in mice. Virol J. 2017;14:242. doi:10.1186/s12985-017-0909-z29273069

 PubMedGoogle Scholar

Park EJ, Choi J, Kim JH, et al. Subchronic immunotoxicity and screening of reproductive toxicity and developmental immunotoxicity following single instillation of HIPCO-single-walled carbon nanotubes: purity-based comparison. Nanotoxicology. 2016;10:1188–1202. doi:10.1080/17435390.2016.120234827310831

 PubMed Web of Science ®Google Scholar

Lee S, Khang D, Kim S-H. High dispersity of carbon nanotubes diminishes immunotoxicity in spleen. Int J Nanomed. 2015;10:2697–2710.

 PubMed Web of Science ®Google Scholar

Bottini M, Bruckner S, Nika K, et al. Multi-walled carbon nanotubes induce T lymphocyte apoptosis. Toxicol Lett. 2006;160:121–126. doi:10.1016/j.toxlet.2005.06.02016125885

 PubMed Web of Science ®Google Scholar

Pietroiusti A, Massimiani M, Fenoglio I, et al. Low doses of pristine and oxidized single-wall carbon nanotubes affect mammalian embryonic development. ACS Nano. 2011;5:4624–4633. doi:10.1021/nn200372g21615177

 PubMed Web of Science ®Google Scholar

Qi W, Bi J, Zhang X, et al. Damaging effects of multi-walled carbon nanotubes on pregnant mice with different pregnancy times. Sci Rep. 2014;4:4352. doi:10.1038/srep0435224619025

 PubMed Web of Science ®Google Scholar

Cheng J, Cheng SH. Influence of carbon nanotube length on toxicity to zebrafish embryos. Int J Nanomed. 2012;7:3731–3739. doi:10.2147/IJN

 PubMed Web of Science ®Google Scholar

Huang X, Zhang F, Sun X, et al. The genotype-dependent influence of functionalized multiwalled carbon nanotubes on fetal development. Biomaterials. 2014;35:856–865. doi:10.1016/j.biomaterials.2013.10.02724344357

 PubMed Web of Science ®Google Scholar

Zhu B, Song Z, Jian L, et al. Developmental toxicity, bioaccumulation and distribution of oxidized single walled carbon nanotubes in Artemia salina. Toxicol Res (Camb). 2018;7:897–906.30310666

 PubMed Web of Science ®Google Scholar

Bai Y, Zhang Y, Zhang J, et al. Repeated administrations of carbon nanotubes in male mice cause reversible testis damage without affecting fertility. Nat Nanotechnol. 2010;5:683–689. doi:10.1038/nnano.2010.15320693989

 PubMed Web of Science ®Google Scholar

Lindberg HK, Falck GC, Singh R, et al. Genotoxicity of short single-wall and multi-wall carbon nanotubes in human bronchial epithelial and mesothelial cells in vitro. Toxicology. 2013;313:24–37. doi:10.1016/j.tox.2012.12.00823266321

 PubMed Web of Science ®Google Scholar