Adsorption and Self-Assembly of Anticancer Antibiotic Doxorubicin on Single-Walled Carbon Nanotubes

Abstract

We performed a combined experimental and theoretical study of the conjugates obtained from single-walled carbon nanotubes and anticancer antibiotic doxorubicin (DOX). Atomic force microscopy (AFM) imaging at lower magnification revealed, extended regions of single-walled carbon nanotubes (SWNTS) fully covered with DOX adsorbed molecules, along with some bare parts without the adsorbed drug, thus suggesting that the DOX adsorption is a cooperative process. Ambient atmosphere scanning tunneling microscopy (STM) at higher resolutions found that individual SWNTs-DOX conjugates exhibit a periodic texture, whose most important morphological feature is alternating depressions and protrusions along the nanotube. Based on the images and profiles measured, we suggest that doxorubicin molecules self-assemble on SWNTs sidewall according to a helical pattern, in which their tetracyclic fragments are turned with respect to the nanotube axis by about 50[Formula: see text]. To provide an additional insight into the structure of noncovalent SWNTs-DOX conjugates, we employed density functional theory (DFT) calculations with three long-range corrected functionals: M05-2X, wB97X-D and LCBLYP, of which M05-2X yielded the most realistic results in terms of geometries and energies.

Doxorubicin Adsorbed on Carbon Nanotubes: Helical Structure and New Release Trigger

“…[25] We interpret them as the conductive tricyclic dihydroxyanthraquinone subunit in Dox, which is hold by π-π interactions on the benzene rings of the CNT. In contrast to Rodriguez-Galvan, [16] we interpret the arrangement of the tricyclic aromatic system as parallel to the CNT axis. Probably the less crowded side of Dox is interacting with the CNT and the sugar moiety is pointing away from the CNT (Figure 2a′,f).…”

“…[3,14] The supramolecular Dox@CNT complex is reasonably stable, has been characterized by many methods, e.g., UV-vis, [3,5,9] Raman, [1] FTIR, [12] and zeta potential, [7,9] and exhibits a large drug loading efficiency, of 70-130%, as measured by UV-vis. [1] Recently, scanning tunneling microscopy (STM) results with molecularly resolved Dox physically adsorbed on CNT have been reported, [16] showing Dox on the cylindrical CNT surface in a helical arrangement with a 50° inclination of Dox with respect to the CNT axis. [5] Transmission electron microscopy (TEM) measurements on the self-assembled systems [7,9,14] show Dox as clusters on CNT, [14] and adsorbed at the interstitial space of helically wrapping polymers, [7,9] as further supported by atomic force microscopy (AFM) [1,3] and (scanning electron microscopy) SEM studies.…”

“…[7,9,15] For additional polyethylene glycol (PEG) functionalized single wall carbon nanotubes loading efficiencies from 50% up to 400% have even been claimed. However, the reported STM image does not reveal structural variability and it cannot explain loading efficiencies in the 100-200% range.Several molecular dynamics (MD), semi-empirical, and density functional theory (DFT)-type calculations and modeling approaches have been applied to Dox [10,16] (or other drugs) [17] on CNT. [1] Recently, scanning tunneling microscopy (STM) results with molecularly resolved Dox physically adsorbed on CNT have been reported, [16] showing Dox on the cylindrical CNT surface in a helical arrangement with a 50° inclination of Dox with respect to the CNT axis.…”

“…Several molecular dynamics (MD), semi-empirical, and density functional theory (DFT)-type calculations and modeling approaches have been applied to Dox [10,16] (or other drugs) [17] on CNT. Rodriguez-Galvan used DFT on a fulleroid/Dox complex The well-known drug delivery system "doxorubicin physically loaded on carbon nanotubes" (Dox@CNT) is visualized by scanning tunneling microscopy at the molecular level, revealing rich architectural variability of Dox@ CNT, and allowing to measure and rationalize reported loading efficiencies (80-200%) for the first time from image analysis.…”

“…[7,9,15] For additional polyethylene glycol (PEG) functionalized single wall carbon nanotubes loading efficiencies from 50% up to 400% have even been claimed. [1] Recently, scanning tunneling microscopy (STM) results with molecularly resolved Dox physically adsorbed on CNT have been reported, [16] showing Dox on the cylindrical CNT surface in a helical arrangement with a 50° inclination of Dox with respect to the CNT axis. [1] Recently, scanning tunneling microscopy (STM) results with molecularly resolved Dox physically adsorbed on CNT have been reported, [16] showing Dox on the cylindrical CNT surface in a helical arrangement with a 50° inclination of Dox with respect to the CNT axis.…”