RESUMO
BACKGROUND: The potential use of carbon nanotubes (CNTs) in gene therapy as delivery systems for nucleic acids has been recently recognized. Here, we describe that metallic versus semiconducting single-wall CNTs can produce significant differences in transfection rate and cellular distribution of siRNA in murine PAM212 keratinocytes. RESULTS/METHODOLOGY: The results of cell interaction studies, coupled with supportive computational simulations and ultrastructural studies revealed that the use of metallic single wall CNTs resulted in siRNA delivery into both the cytoplasm and nucleus of keratinocytes, whereas semiconducting CNTs resulted in delivery only to the cytoplasm. CONCLUSION: Using enriched fractions of metallic or semiconducting CNTs for siRNA complex preparation may provide specific subcellular targeting advantages.
RESUMO
Tubulin, the structural subunit of microtubules, is the target of some highly successful anti-tumor drugs. Most of these drugs bind to the beta-tubulin resulting in the inhibition of microtubule dynamics and eventually cell death. The varied cellular distribution of several human isotypes of beta -tubulin provides a platform upon which to construct novel chemotherapeutic agents that are able to differentiate between these types of cells. To test this hypothesis, we have previously created homology models of the nine most frequently observed human beta -tubulin isotypes and analyzed them for differences in the colchicine-binding site. Here, we describe the electrostatic properties of the colchicine binding site and how this may affect calculated drug binding affinities between the beta -tubulin isotypes.
