Role of systemic T-cells and histopathological aspects after subcutaneous implantation of various carbon nanotubes in mice
Introduction
Much attention has been paid on the tiny but interesting sp2-based carbon nanotubes (CNTs), due to their small size and extraordinary physicochemical properties which make them useful in a wide range of applications from nanocomposites, sensor, electronic nano-device, electrochemical system to medical device such as micro-catheter [1], [2], [3], [4]. These days, large quantity of carbon nanotubes is available due to the establishment of well-developed chemical vapor deposition (CVD) method, especially using the floating reactant method [5], [6]. In this sense, the toxicology of these CNTs has to be evaluated under environmental and occupational exposure including biocompatibility. It is expected that their intrinsic features, derived from the nano-scale and high aspect ratio (above 100), gives rise to different biological effects compared to micro- and macro-materials, even though conventional carbon materials have extremely high level of biocompatibility as used for artificial heart valves.
Unfortunately, there have been limited studies available on the toxicology of nano-sized materials including CNTs, as compared with that of asbestos [7], [8]. Recently published studies on pulmonary toxicity of CNTs proved that inhaled CNTs induced the formation of epithelial granulomas and inflammation [9], [10]. Furthermore, it is suggested that some nanoparticles might be toxic to human keratinocytes [11]. When considering application of CNTs especially in biomedical engineering and in vivo chemistry, their biocompatibility have to be evaluated clearly because CNTs exhibited cytotoxicity to human keratinocyte cells [11], [12], have inhibited the growth of embryonic rat-brain neuron cells [13] and have induced formation of lung granulomas in mice [9], [10], [14]. Therefore, it is essential that their biocompatibility and also their potential toxicity be investigated systematically. Here, we report time-dependent changes in CD4+ and CD8+ T-cells, and also pathological differences between four different types of CNTs ranging from single-walled carbon nanotubes (SWNTs), two types of multi-walled carbon nanotubes with different diameters (MWNTs-I = ca. 20 nm in diameter, MWNTs-II = ca. 80 nm in diameter) to cup-stacked type carbon nanotubes (CSNTs) after the subcutaneous implantation for 3 months in mice [8], [15]. Our basic study will contribute to the intensified research and development of CNTs not only in engineering fields but also in medical and biology areas under suitable handling of CNTs.
Section snippets
CNT materials
High purity SWNTs were obtained through a combination of catalytic CVD method and optimized purification method [16]. They are self-assembled into a bundle structure (Fig. 1(a)) while a detailed high-resolution transmission electron microscope (HR-TEM) study revealed that their diameters are generally in the range from 0.8 to 2.0 nm (Fig. 1(b)). Two types of MWNTs with different diameters ranges (I = 20–70 nm and II = 50–150 nm) were chosen as samples, which were obtained by catalytic CVD method by
Body weight
All animals survived the test period. In addition, no large changes in body weight of animals for all groups versus control indicate a good standard development within our experimental time (up to 3 months) (Fig. 2). As a comparative standard (control), values of CD4+ T-cells at 1, 2, 3 weeks, 1 month, 2 months and 3 months post-implantation were 30.7 ± 4.9%, 36.3 ± 2.2%, 27.2 ± 3.3%, 32.4 ± 0.6%, 40.9 ± 2.31% and 28.9 ± 3.9% while values of CD8+ T-cells at same time were 11.1 ± 0.9%, 11.6 ± 0.4%, 16.3 ± 2.9%,
Discussion
In this study, by using peripheral T-cell in combination with histological study, we have investigated the biological response to four types of carbon nanotubes. CNTs used here gave rise to several characteristic time-dependent changes in CD4+- and CD8+ T-cells. In addition, these changes are strongly dependent upon the post-implantation time. From these experimental results, when evaluating toxicology of CNTs, we should consider several important facts, such as the physiochemical properties of
Acknowledgements
This work was supported by the CLUSTER of Ministry of Education, Culture, Sports, Science and Technology and a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan (No. 16201024).
References (28)
- et al.
Filamentous growth of carbon through benzene decomposition
J Crys Growth
(1976) - et al.
Vapor-grown carbon fibers (VGCFs): Basic properties and their battery application
Carbon
(2001) - et al.
An introduction to the short-term toxicology of respirable industrial fibres
Mutat Res
(2004) - et al.
Structural characterization of carbon nanofibers obtained by hydrocarbon pyrolysis
Carbon
(2001) - et al.
Synthesis and structural characterization of thin multi-walled carbon nanotubes with a partially facetted cross section by a floating reactant method
Carbon
(2005) - et al.
Reactive oxygen species in pulmonary inflammation by ambient particulates
Free Radic Biol Med
(2003) - et al.
The response to the intramuscular implantation of pure metals
Biomaterials
(1981) - et al.
Generation of CD8 (T8) cytotoxic cells has a preferential requirement for CD4+ 2H4− inducer cells
Cell Immunol
(1988) - et al.
Effect of single wall carbon nanotubes on human HEK293 cells
Toxicol Lett
(2005) - et al.
Multi-walled carbon nanotube interactions with human epidermal keratinocytes
Toxicol Lett
(2005)
Science of fullerenes and carbon nanotubes
Thrombogenicity and blood coagulation of a microcatheter prepared from carbon nanotube-nylon-based composite
Nano Lett
Growth of vapor-grown carbon fibers using fluid ultra-fine particles of metals
Jap J Appl Phys
Grow carbon fibers in the vapor phase
Chem Tech
Cited by (78)
CARBON-BASED nanomaterials and SKIN: An overview
2022, CarbonCarbon nanotubes: Evaluation of toxicity at biointerfaces
2019, Journal of Pharmaceutical AnalysisFunctionalized carbon nanotubes as emerging delivery system for the treatment of cancer
2018, International Journal of PharmaceuticsUHMWPE Matrix Composites
2016, UHMWPE Biomaterials Handbook: Ultra High Molecular Weight Polyethylene in Total Joint Replacement and Medical Devices: Third EditionUHMWPE Matrix Composites
2015, UHMWPE Biomaterials Handbook: Ultra High Molecular Weight Polyethylene in Total Joint Replacement and Medical DevicesEvaluation of carbon nanotubes and graphene as reinforcements for UHMWPE-based composites in arthroplastic applications: A review
2014, Journal of the Mechanical Behavior of Biomedical Materials