Accumulation of intravenously injected carboxylated single-walled carbon nanotubes in rat axillary lymph nodes

doi:10.3969/j.issn.2095-4344.2015.25.011

Abstract

Abstract:

BACKGROUND: Lymph-targeted tracing and therapy based on carbon nanotubes have been one of the hottest researches on targeting tumor diagnosis and treatment. To evaluate the accumulation of carbon nanotubes in axillary lymph node can provide experimental evidences for developing nano-tracers and drug carriers which are more lymph-specific and more biocompatible.
OBJECTIVE: To study the accumulation of the intravenously injected carboxylated single-walled carbon nanotubes in axillary lymph nodes of Sprague-Dawley rats, and to evaluate their effect on blood cells.
METHODS: Sixty-four Sprague-Dawley rats were randomly divided into two groups. Rats in testing group were injected with carboxylated single-walled carbon nanotubes suspension (2 mg/kg), while those in control group were injected with 5% glucose solution (1 mL/kg), both through the tail vein, three times per week. Four periods of 7, 60, 90 and 120 days were set (the 120-day period referred to 90 days of administration followed by 30 days of
drug withdrawal). At the end of each period, eight rats from each group were randomly picked out, to collect blood samples via the abdominal aorta for blood routine test. Finally the axillary lymph nodes were observed, and the lymph node samples of rats in the testing group were collected and analyzed at 120 days by transmission electron microscope.
RESULTS AND CONCLUSION: Compared with the control group, black staining of axillary lymph nodes of rats in testing group was not obvious at the end of the 7-day period. However, with the increase of the dosing periods, the lymph nodes of the rats in the testing group became enlarged, firm and black stained, coupled with a significant rising in the percentage of blood neutrophils. After 30 days of drug withdrawal, the size of the rat axillary lymph nodes was reduced and black staining partly faded, with the decreasing of blood neutrophil percentage. Under the transmission electron microscope, abundant carboxylated single-walled carbon nanotubes were uptaken by lymphocytes to form a large number of phagocytic vacuoles after drug withdrawal for 30 days. It indicates that the short-term tracing of rat axillary lymph nodes by carboxylated single-walled carbon nanotubes injected through the tail vein is relatively weak, while the long-term intravenous injection can cause their accumulation in rat axillary lymph nodes, coupled with the increase of neutrophils; after drug withdrawal, the carboxylated single-walled carbon nanotubes can be slowly cleared by the lymph nodes.

中国组织工程研究杂志出版内容重点：生物材料；骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性；组织工程

Key words: Nanotubes, Carbon, Lymph Nodes, Lymphocytes

CLC Number:

R318

Li Su-ning, Qin Yue, Cheng Xiao-jing, Fu Xuan-hao, Feng Jian-hai, Lai Ze-feng, Liu Hua-gang. Accumulation of intravenously injected carboxylated single-walled carbon nanotubes in rat axillary lymph nodes [J]. Chinese Journal of Tissue Engineering Research, 2015, 19(25): 3990-3995.

Figures/Tables 5

References

[1] Manojit P,Kwang HS,Magdalena S,et al.In vivo carbon nanotube-enhanced non-invasive photoacoustic mapping of the sentinel lymph node.Phys Med Biol.2009;54:3291-3301.

[2] Feng Y,Jianhua H,Dong Y,et al.Pilot study of targeting magnetic carbon nanotubes to lymph nodes.Nanomedicine (Lond).2009;4(3):317-330.

[3] Feng Y,Chen J, Dong Y,et al.Magnetic functionalised carbon nanotubes as drug vehiclesfor cancer lymph node metastasis treatment.Eur J Cancer.2011;47:1873-1882.

[4] Chao L,Shuo D,Chao W,et al.Tumor metastasis inhibition by imaging-guided photothermal therapy with single-walled carbon nanotubes.Adv Mater.2014;26(32): 5646-5652.

[5] 李林茂,赖泽锋,李苏宁,等.利用斑马鱼胚胎初步评价单壁碳纳米管的生物毒性[J].广西医科大学学报,2013,30(3):332-336.

[6] Wong BS,Yoong SL,Jagusiak A,et al.Carbon nanotubes for delivery of small molecule drugs.AdvDrug Deliv Rev.2013; 65(15):1964-2015.

[7] Joshua TR,Guosong H,Yongye L,et al.In Vivo fluorescence imaging in the second near-infrared window with long circulating carbon nanotubes capable of ultrahigh tumor uptake.J Am Chem Soc.2012;134(25):10664-10669.

[8] Guosong H,Shuo D,Junlei C,et al.Through-skull fluorescence imaging of the brain in a new near-infrared window.Nat Photonics.2014;8:723-730.

[9] 金彦召,谭敏.磁性碳纳米管载附5-氟尿嘧啶对结肠癌淋巴结转移的靶向抑制作用[J].中国组织工程研究,2012,16(16): 2884- 2888.

[10] Xiaoning C,Rajkumar R,Hau SW,et al.Characterization of carbon nanotube protein corona by using quantitative proteomics.Nanomed Nanotechnol.2013;9:583-593.

[11] Hélène D.When carbon nanotubes encounter the immune system: desirable and undesirable effects.Adv Drug Deliver Rev.2013;65:2120-2126.

[12] Naihao L,Jiayu L,Rong T,et al.Binding of human serum albumin to single-walled carbonnanotubes activated neutrophils to increase production of hypochlorous acid, the oxidant capable of degrading nanotubes.Chem Res Toxicol. 2014;27:1070-1077.

[13] Zhuang L,Corrine D,Weibo C,et al.Circulation and long-term fate of functionalized,biocompatible single-walled carbon nanotubes in mice probed by Raman spectroscopy. P Natl Acad Sci USA.2008;105(5): 1410-1415.

[14] Marco O,Davide B,Francesco S,et al.Impact of carbon nanotubes and graphene on immune cells.J Transl Med. 2014;12:138-148.

[15] 刘元方,刘佳蕙,王海芳.未修饰碳纳米管的细胞毒性机理及其影响因素[J].上海大学学报,2010,16(5):337-349.

[16] Soyoung L,Dongwoo K,Sang-Hyun K.High dispersity of carbon nanotubes diminishes immunotoxicity in spleen.Int J Nanomed.2015;10:2697-2710.

[17] Ningning G,Qiu Z,Qingxin M,et al.Steering carbon nanotubes to scavenger receptor recognition by nanotube surface chemistr modification partially alleviates NFκB activation and reduces its immunotoxicity.ACS NANO.2011;5(6):4581-4591.