(ii) The DNA strands also provide very stable interaction with CNT surface and help to control the length of the tubes [18]. Because DNA-CNT binding energy is fairly large, “fortification” of the nanotube segments covered by DNA is expected. When the CNT breakage occurs (e.g.,

because of thorough sonication [17]), it will take place in the regions with Inhibitors,research,lifescience,medical a lower tensile strength, that is, the uncovered parts of the nanotube, leaving the tubes of the length of the DNA-wrapped structures. All these features are very important for medical applications, since it has been shown that shortened, better isolated and dispersed, functionalized CNTs demonstrate an Inhibitors,research,lifescience,medical improved toxicological profile in in vivo studies [19–22]. It is widely recognized that structural and surface

characteristics of DDS should critically influence their biological performance. Yet little is known about the detailed structure of CNT-DNA hybrids. Different computational approaches reported in the Inhibitors,research,lifescience,medical literature predict a large variation of the possible DNA binding geometries [23] from linear DNA alignment along the CNT [24] to wrapping of DNA around the CNT [25], with a finite probability of the DNA insertion into the interior volume of the CNT [26, 27]. In addition, recent experimental studies have empirically demonstrated that DNA oligomers with a particular sequence prefer to

form stable structures with a specific kind of nanotubes and ignore others. These observations suggest that the chemical structure of DNA and the chirality Inhibitors,research,lifescience,medical of the CNT play a significant, if not determining, role in establishing the final hybrid geometry [16, 28, 29]. Unfortunately, the current theoretical framework cannot explain the wide geometry variations and sequence selectivity of the DNA-CNT binding. Additional complexity comes Inhibitors,research,lifescience,medical from the lack of understanding of the exact mechanisms of cellular membrane penetration by CNTs [12, 30]: it is unclear how the given hybrid structure influences penetration efficiency, as well as how the penetration process influences stability of a hybrid too DDS. As such, new methods have to be developed for reliable prediction of the properties of DDS based on CNT-DNA hybrids and accurate control of drug binding and delivery. Considering its importance, the stability of DNA coating of the nanotube surface has to be analyzed in order to avoid the risk of macromolecule desorption or exchange with serum proteins and other blood components following administration. Hence, theoretical modeling and simulations capable of describing the DNA-CNT binding mechanisms and predicting the hybrid stable structure and its relevant properties will significantly benefit experimental in vitro and in vivo studies of MGCD0103 CNT-DNA-based DDS.