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

Abstract

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).

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

“…The state in Figure 2B shows that the iM chains tend to separate from each other in the bulk and approach the nanotube surface. A similar phenomenon was also observed in our earlier study [22] concerning interaction of free telomeric cytosine-rich DNA fragments with surfaces of carbon nanotubes. It turned out that these DNA fragments rather weakly adsorb on the CNT surface and are able to detach from the surface and exist in the bulk as free molecules.…”

“…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.…”

“…In one of our recent papers, we analyzed and discussed the properties of a system composed of a carbon nanotube and co-adsorbed DOX and iM sequences [22]. That model revealed that binding of iM to carbon nanotube surface depends strongly on the presence of DOX and folding/unfolding of iM.…”

Mechanistic Understanding From Molecular Dynamics Simulation in Pharmaceutical Research 1: Drug Delivery

“…Carbon Dots - (Erimban and Daschakraborty, 2020) Carbon Nanotubes - (Panczyk et al, 2013(Panczyk et al, , 2020Izadyar et al, 2016;Li et al, 2016a;Rungrotmongkol and Poo-arporn, 2016;Hashemzadeh and Raissi, 2017;Kamel et al, 2017;Wolski et al, 2017aWolski et al, , 2018Wolski et al, , 2020Wolski et al, , 2019Zaboli and Raissi, 2017;Karnati and Wang, 2018;Kavyani et al, 2018a,b;Zhang et al, 2018;Contreras et al, 2019;Dehneshin et al, 2019;Mortazavifar et al, 2019;Kordzadeh et al, 2019;Ghadri et al, 2020;Maleki et al, 2020;Pakdel et al, 2020;Pennetta et al, 2020) Dendrimers - (Kojima et al, 2000;Lee et al, 2002Maiti and Bagchi, 2006;Lee and Larson, 2008Vasumathi and Maiti, 2010;Nandy and Maiti, 2011;Huynh et al, 2012;Nandy et al, 2012Nandy et al, , 2013Jain et al, 2013Jain et al, , 2016Kłos and Sommer, 2013;Tian and Ma, 2013;Tu et al, 2013;Martinho et al, 2014;Wen et al, 2014;Jiang et al, 2015;…”

Doxorubicin Encapsulation in Carbon Nanotubes Having Haeckelite or Stone–Wales Defects as Drug Carriers: A Molecular Dynamics Approach

“…CNTs form stable associations with doxorubicin [ 7 ]. Various theoretical and molecular dynamics studies predict a high capacity of CNTs as carriers [ 20 , 31 , 32 , 33 , 34 , 35 , 36 ] and several molecular dynamics studies of functionalized DOX-CNT systems with various organic groups have contributed to the study of DOX loading and release [ 37 , 38 , 39 , 40 , 41 , 42 , 43 ]. Although there are several works on the adsorption of DOX in CNT, there are no studies that report on the optimal structure that a nanotube should have to behave as a DOX nanocarrier.…”