Curing the Toxicity of Multi-Walled Carbon Nanotubes through Native Small-molecule Drugs

Abstract

With the development and application of nanotechnology, large amounts of nanoparticles will be potentially released to the environment and possibly cause many severe health problems. Although the toxicity of nanoparticles has been investigated, prevention and treatment of damages caused by nanoparticles have been rarely studied. Therefore, isotope tracing and improved CT imaging techniques were used to investigate the biodistribution influence between oMWCNTs(oxidized multi-walled carbon nanotubes) and 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC)/or simvastatin (TD) in vivo. What's more, biochemical indices in plasma and tissue histology were measured to further study therapeutic effects on the damages of oMWCNTs in mice. Isotope tracing and improved CT imaging results showed that low dosages of DOPC and TD didn't affect the distribution of oMWCNTs in mice; conversely, the distribution and metabolism of DOPC and TD were influenced by oMWCNTs. Moreover, DOPC and/or TD improved the biocompatibility of oMWCNTs in erythrocyte suspension in vitro. Biochemical index and histopathological results indicated that DOPC and TD didn't prevent injuries caused by oMWCNTs effectively. But TD showed a good therapeutic effect for damages. This study is the first to investigate prevention and treatment effects of drugs on damages caused by oMWCNTs and provides new insights and breakthroughs for management of nanoparticles on health hazards.

Figure 1

Biodistribution interaction effect of DOPC/or TD on oMWCNTs during 24 h after exposure to mice (A and B for ¹³¹I-oMWCNTs + DOPC and ¹³¹I-DOPC + oMWCNTs respectively, C and D for ¹³¹I-oMWCNTs + TD and ¹³¹I-TD + oMWCNTs, n = 5, +sem).

Figure 2

The CT imaging of Ag/oMWCNTs in mice with affection by different dosage of DOPC/or TD (A,B,C is the whole CT imaging of mice after exposure saline solution, single Ag nanoparticles, Ag/oMWCNTs, respectively; (a,b,c) is the lung CT imaging for control, single Ag nanoparticles and Ag/oMWCNTs, respectively; (D,E,F) is the whole CT imaging and (d,e,f) is the lung CT imaging of mice after exposure 6.2, 12.4 and 18.6 mg/kg.bw TD to oMWCNTs-model mice, respectively; (G,H,I) is the whole CT imaging and (g,h,i) is the lung CT imaging of mice after exposure 6.2, 12.4 and 18.6 mg/kg.bw DOPC to oMWCNTs-model mice, respectively).

Figure 3

The biochemical indices level of BUN (blood urea nitrogen), CREA (creatinine), AST (aspartate aminotransferase), Cys-C (cystatin C), ALT (alanine aminotransferase) and TB (total bilirubin) change in plasma after exposure different dosages of 6.2, 18.6, 31 mg/kg.bw oMWCNTs to mice (*p < 0.05 for groups vs. control group; ^& p < 0.05 for groups vs. 6.2 mg/kg.bw-group; ^$ p < 0.05 for groups vs. 12.4 mg/kg.bw-group; n = 5, +sem).

Figure 4

The biochemical indices level of BUN (blood urea nitrogen), CREA (creatinine), AST (aspartate aminotransferase), Cys-C (cystatin C), ALT (alanine aminotransferase), CRP (C-reaction protein) and TB (total bilirubin) change in plasma after exposure DOPC/or TD to oMWCNTs–model mice (*p < 0.05 for groups vs. control group; ^& p < 0.05 for groups vs. oMWCNTs-model group; n = 5, +sem).

Figure 5

The tissue histology (200×, scale bar is 50 μm for B–G groups, and scale bar is 100 μm for A group) investigation after exposure different drugs (A1–A5 for tissues of heart, liver, spleen, lung and kidney of control group mice, respectively; B1-B5 for tissues of heart, liver, spleen, lung and kidney of oMWCNTs-model group mice, respectively; C1–C5 for tissues of heart, liver, spleen, lung and kidney of oMWCNTs-model + DOPC group mice, respectively; D1–D5 for tissues of heart, liver, spleen, lung and kidney of oMWCNTs-model + TD group mice, respectively; E1–E5 for tissues of heart, liver, spleen, lung and kidney of TD-model + oMWCNTs group mice, respectively; F1–F5 for tissues of heart, liver, spleen, lung and kidney of DOPC-model + oMWCNTs group mice, respectively; G1–G5 for tissues of heart, liver, spleen, lung and kidney DOPC + oMWCNTs group mice, respectively; H1–H5 for tissues of heart, liver, spleen, lung and kidney of TD + oMWCNTs group mice, respectively).

Figure 6

The biochemical indices level of BUN (blood urea nitrogen), CREA (creatinine), AST (aspartate aminotransferase), Cys-C (cystatin C), ALT (alanine aminotransferase), CRP (C-reaction protein) and TB (total bilirubin) change in plasma after exposure oMWCNTs to DOPC/or TD –model mice (*p < 0.05 for groups vs. control group; ^& p < 0.05 for groups vs. single oMWCNTs group; n = 5, +sem).

Figure 7

The biochemical indices level of BUN (blood urea nitrogen), CREA (creatinine), AST (aspartate aminotransferase), Cys-C (cystatin C), ALT (alanine aminotransferase), CRP (C-reaction protein) and TB (total bilirubin) change in plasma after exposure oMWCNTs and DOPC/or TD to mice simultaneously (*p < 0.05 for groups vs. control group; ^& p < 0.05 for groups vs. single oMWCNTs group; n = 5, +sem).

Figure 8

The biochemical indices level of BUN (blood urea nitrogen), CREA (creatinine), AST (aspartate aminotransferase), Cys-C (cystatin C), ALT (alanine aminotransferase), CRP (C-reaction protein) and TB (total bilirubin) change in plasma after exposure 3.1, 6.2, 9.3 and 18.6 mg/kg.bw TD to oMWCNTs-model mice (*p < 0.05 for groups vs. control group; ^& p < 0.05 for groups vs.single oMWCNTs group; n = 5, +sem).

Figure 9

The cell morphology of erythrocytes under optical microscope (100×, scale bar is100 μm) and SEM (5–10 μm) after exposure saline solution, oMWCNTs, oMWCNTs + DOPC and oMWCNTs + TD to erythrocytes, respectively.