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

Pawel Wolski,Krzysztof Nieszporek,Tomasz Panczyk

doi:10.3390/ijms22168466

Abstract

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.

Highlights

Biomedical applications of carbon nanotubes, CNT, have been considered in literature for many years mainly in the context of tissue engineering, sensing, diagnostic and as therapeutic or teranostic agents [1,2,3]
This is because such oligonucleotides reveal interesting properties of reversible folding/unfolding in response to pH change
We were considering a single walled carbon nanotube with chirality (20.0), which was covalently functionalized by cytosine-rich DNA fragments, iM, on the tips

Summary

Introduction

Biomedical applications of carbon nanotubes, CNT, have been considered in literature for many years mainly in the context of tissue engineering, sensing, diagnostic and as therapeutic or teranostic agents [1,2,3]. Among many papers discussing promising properties of such systems interesting are studies related to telomeric DNA fragments interacting with carbon nanotubes. Application of cytosine-rich telomeric fragments of DNA as components of drugs carriers has been described in several studies [16,17,18,19,20,21,22]. This is because such oligonucleotides reveal interesting properties of reversible folding/unfolding in response to pH change. The i-motif can unfold into a hairpin or random coil [24] spontaneously after bringing pH to ca. 7 and the folding/unfolding transition can be repeated again by switching the pH of solution

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Conclusion