Molecular Dynamics Modeling of the Encapsulation and De-encapsulation of the Carmustine Anticancer Drug in the Inner Volume of a Carbon Nanotube

5 years ago

Molecular Dynamics Modeling of the Encapsulation and De-encapsulation of the Carmustine Anticancer Drug in the Inner Volume of a Carbon Nanotube

Jolanta Narkiewicz-Michalek, Tomasz Panczyk, Giorgia Pastorin, Monika Panczyk, Pawel Wolski

This work deals with the design of a nanocontainer that is able to carry hydrolytically labile molecules like carmustine, undergo selective endocytosis by cancer cells, and de-encapsulate its cargo on demand by application of an external magnetic field. The molecular architecture of the nanocontainer does not differ much from the already known and experimentally characterized systems designed for the realization of stimuli-responsive anticancer drugs carriers. It comprises a carbon nanotube (for the encapsulation of drug molecules in its inner volume) and functionalized nanoparticles, which act as caps to the nanotube and are linked with the nanotube tips by linkers containing hydrazone bonds fragments. At acidic pH, the hydrazone bonds hydrolyze, and the nanotube should be uncapped as the nanoparticles are no longer covalently linked with the nanotube. This simple mechanism is, however, not always operational due to the significant role of nonbonded interactions between the nanotube and the nanoparticles. Our model utilizes the functionalized magnetic nanoparticles as caps to the nanotube, and therefore the nanocontainer becomes sensitive to the external magnetic field. In order to study how the magnetic field affects the state of the nanocontainer, we developed a dedicated molecular dynamics code for the description of the magnetization reversal and coupled it with the standard code of the Newtonian dynamics. The obtained results imply that very small magnetic nanoparticles produce too weak torques on the nanoparticles, and therefore no changes in the molecular structure of the nanocontainer occur. On the other hand, larger nanoparticles with radii > ∼35 Å absorb huge amounts of energy from the magnetic field and produce rapid turns of the nanoparticles. This leads to the uncapping of the nanotube and de-encapsulation of the drug molecules. Moreover, the system containing magnetic nanoparticles can additionally realize magnetic hyperthermia and can be visualized in magnetic resonance imaging. Therefore, the proposed architecture of the nanocontainer represents very promising and useful construction of a stimuli-responsive drug carrier.

Publisher URL: http://dx.doi.org/10.1021/acs.jpcc.7b05229

DOI: 10.1021/acs.jpcc.7b05229