Tissue histology and physiology following intravenous administration of different types of functionalized multiwalled carbon nanotubes.
BACKGROUND
Carbon nanotubes (CNTs) constitute one of the most important types of nanomaterials, increasingly gaining interest as tools for nanomedicine applications, such as sensors, implants or delivery systems. Our groups have reported previously that chemical functionalization of CNTs can lead to their almost complete elimination from the body of animals through the urinary excretion route. The administration of CNTs may, however, impact the physiological function of organs through which CNTs traverse or accumulate.


OBJECTIVE
The present study addresses the short-term impact (first 24 h) of intravenous administration of various types of multiwalled nanotubes (MWNTs) on the physiology of healthy mice.


METHODS
Nonfunctionalized, purified MWNTs (pMWNTs) and different types of water-dispersible, functionalized MWNTs (f-MWNTs) were tail-vein injected. Histological examination of tissues (kidney, liver, spleen and lung) harvested 24 h post-administration indicated that organ accumulation depended on the degree of ammonium (NH(3)(+)) functionalization at the f-MWNT surface.


RESULTS
The higher the degree of functionalization of MWNT-NH(3)(+), the less their accumulation in tissues. pMWNTs coated with autologous serum proteins prior to injection accumulated almost entirely in the lung and liver in large dark clusters. Moreover, various indicators of serum and urine analyses also confirmed that MWNT-NH(3)(+) injections did not induce any physiological abnormality in all major organs within the first 24 h post-injection. Interestingly, no abnormalities were observed either for f-MWNTs highly functionalized with carboxylate groups (diethylentriaminepentaacetic-functionalized MWNTs) or by upscaling to the highest doses ever injected so far in vivo (20 mg/kg).


CONCLUSIONS
The high degree of f-MWNT functionalization responsible for adequate individualization of nanotubes and not the nature of the functional groups was the critical factor leading to less tissue accumulation and normal tissue physiology at least within the first 24 h post-administration, even at the highest carbon nanotube doses ever administered in any study today.
Lacerda
Lara
L
The School of Pharmacy, University of London, Nanomedicine Laboratory, Centre for Drug Delivery Research, London WC1N 1AX, UK.
Ali-Boucetta
Hanene
H
Herrero
Maria A
MA
Pastorin
Giorgia
G
Bianco
Alberto
A
Prato
Maurizio
M
Kostarelos
Kostas
K
D000818:Animals; D005260:Female; D007275:Injections, Intravenous; D051379:Mice / Q000033:anatomy & histology* / Q000378:metabolism*; D008807:Mice, Inbred BALB C; D037742:Nanotubes, Carbon / Q000032:analysis*; D009928:Organ Specificity; D014018:Tissue Distribution
D037742:Nanotubes, Carbon