Cytosine-Rich DNA Fragments Covalently Bound to Carbon Nanotube as Factors Triggering Doxorubicin Release at Acidic pH. A Molecular Dynamics Study

This works deals with analysis of properties of a carbon nanotube, the tips of which were functionalized by short cytosine-rich fragments of ssDNA. That object is aimed to work as a platform for storage and controlled release of doxorubicin in response to pH changes. We found that at neutral pH, doxorubicin molecules can be intercalated between the ssDNA fragments, and formation of such knots can effectively block other doxorubicin molecules, encapsulated in the nanotube interior, against release to the bulk. Because at the neutral pH, the ssDNA fragments are in form of random coils, the intercalation of doxorubicin is strong. At acidic pH, the ssDNA fragments undergo folding into i-motifs, and this leads to significant reduction of the interaction strength between doxorubicin and other components of the system. Thus, the drug molecules can be released to the bulk at acidic pH. The above conclusions concerning the storage/release mechanism of doxorubicin were drawn from the observation of molecular dynamics trajectories of the systems as well as from analysis of various components of pair interaction energies.

Automated summary

The study analyzed the properties of a carbon nanotube functionalized with short cytosine-rich fragments of ssDNA for the storage and controlled release of doxorubicin in response to pH changes. It was found that at neutral pH, doxorubicin molecules can be effectively intercalated between ssDNA fragments for storage, while at acidic pH, the molecules can be released due to structural changes in the ssDNA fragments.