Interaction between kupffer cells and carbon nanotubes-transition from biodistribution and toxicity to Kupffer cell targeted therapy.

. The Kupffer (KCs) cells play the major role in the pathogenesis of chronic liver diseases, initiating and maintaining the inflammation and activation of the hepatic stellate cells (HSCs), events leading finally to liver parenchyma fibrosis and cirrhosis. The previous biodistribution studies showed an intense uptake of nanoparticles with specific characteristics and functional groups in the hepatic Kupffer (KCs), showing the major potential of these types of carriers for targeted therapy in liver inflammatory and storage disorders. In vivo uptake of Single and Multi-wall Carbon Nanotubes by the hepatic cells was tested, assessing the potential use of the ss-DNA-SWCNT as drug carriers for Kupffer cells targeted drug delivery. The changes in terms of histology, histochemistry and apoptosis were determined in liver in order to assess the local toxic effect. Fluorescently labeled Single Wall Carbon Nanotubes were injected intraperitoneally (IP) in rats and traced by CLSM and histology in terms of distribution and amount in the liver tissue. In the present experiment we determined the rapid and intense accumulation of both forms of CNT in Kupffer cells comparing with hepatocytes and endothelial cells, probing a strong and specific interaction of ss-DNA labeled nanoparticles with Kupffer cells. Discreet changes in the histology, histochemistry and caspase3 expression was observed. The strong Kupffer cell-associated nanoparticle distribution and the low toxicity at our tested dose open the possibilities of using this form of nanoparticle and functional group as nanocarriers for specific drug delivery in the hepatic Kupffer cells.