Carbon Nanotubes and Short Cytosine-Rich Telomeric DNA Oligomeres as Platforms for Controlled Release of Doxorubicin-A Molecular Dynamics Study.

This work deals with molecular dynamics analysis of properties of systems composed of carbon nanotubes and short telomeric DNA strands able to fold into i-motif structures at slightly acidic pH conditions. The studies are focused on possible application of such constructs as pH-controlled drug delivery and release systems. We study two different approaches. The first assumes that folding/unfolding property of these DNA strands might realize a gate closing/opening mechanism with carbon nanotube as a container for drug molecules. The second approach assumes that these DNA strands can modulate the drug intercalating property as a function of pH. As a model drug molecule we used doxorubicin. We found that the first approach is impossible to realize because doxorubicin is not effectively locked in the nanotube interior by DNA oligonuceotides. The second approach is more promising though direct drug release was not observed in unbiased molecular dynamics simulations. However, by applying detailed analysis of pair interaction energies, mobilities and potential of mean force we can show that doxorubicin can be released when the DNA strands fold into i-motifs. Carbon nanotube in that latter case acts mainly as a carrier for active phase which is composed of DNA fragments able to fold into noncanonical tetraplexes (i-motif).