Understanding the co-loading and releasing of doxorubicin and paclitaxel using chitosan functionalized single-walled carbon nanotubes by molecular dynamics simulations

Abstract

Two widely used anticancer drugs, doxorubicin (DOX) and paclitaxel (PTX), possess distinct physical properties and chemotherapy specificity. In order to investigate their interaction mechanism with single-walled carbon nanotubes (SWCNTs), co-loading and releasing from the SWCNTs, all-atom molecular dynamics (MD) simulations were firstly carried out for different SWCNT systems, followed by binding free energy calculation with MM-PBSA. The results indicate that the co-loading of DOX and PTX onto the pristine SWCNT is exothermic and spontaneous. The DOX molecules predominantly interact with the SWCNT via π-π stacking through the conjugated aromatic rings, while the separated aromatic rings of PTX also primarily interact with the SWCNT through π-π stacking yet supplemented by an X-π (X = C-H, N-H and C[double bond, length as m-dash]O) interaction. Moreover, the strongest binding of DOX and PTX with the pristine SWCNT shows similar strength (ΔG: -32.0 vs. -33.8 kcal mol-1). For the chitosan functionalized SWCNT (f-SWCNT), the DOX and PTX molecules still prefer binding to the sidewall of the CNT rather than binding with the polymer, and the non-covalent functionalization of the SWCNT with chitosan decreases the binding of DOX and PTX with the sidewall of the f-SWCNT as compared with the DOX/PTX-SWCNT system (ΔG: -24.0 and -21.9 kcal mol-1). The protonation of chitosan and drug molecules further weakens the interaction between DOX/PTX and the f-SWCNT, and shows a consequent displacement of the drug molecules, triggering the release of the drugs. The variation of binding strength of the three systems (DOX/PTX-SWCNT, DOX/PTX-f-SWCNT, and DOXH+/PTXH+-f-SWCNT) was also discussed in terms of the histogram or frequency of the distance from the drugs to the SWCNT. In addition, the encapsulation of two DOX molecules by the f-SWCNT is considerably stronger than the binding of the other six drug molecules to the sidewall, indicating that the encapsulation of anticancer drugs may also play a very important role and should be considered in the drug delivery.

Atomistic insight into novel co-delivery of doxorubicin and paclitaxel using fullerene modified by dimethyl acrylamide trimethyl chitosan: A computational study

“…Simulation results yielded a ∆G value of -21.64 kcal/mol that was near that of the reference study. These measurements can provide proof of this work and show consistency with previous works (38).…”

“…To validate the computational procedure, a relevant recent article was chosen to reproduce a part of Gibbs free energy (∆G) calculation (38). This article has studied the co-delivery of DOX/PAX by a nanotube-chitosan carrier.…”

“…However, therefore, the C60s as an attractive carrirer for drug release were used to compare the uptake, diffusion, and release of DOX and PAX from C60 in the presence of chitosan polymer. Given the unique properties of C60, this could be an excellent introduction to the wider use of carbon C60 in the loading and release of anticancer drugs (38).…”

The Advances in Biomedical Applications of Carbon Nanotubes

“…The study showed pH-dependent drug release potential and anti-cancer activity of CNTs loaded with curcumin. Apart from curcumin, there is a range of studies demonstrating that anticancer herbal compounds can be effectively combined with CNTs: paclitaxel [80,81], docetaxel [82], vinca alkaloids [83], camptothecin [84,85], podophyllotoxin [86], quercetin [87], oridonin [88], etc.…”

Synergistic inhibition of metastatic breast cancer by dual-chemotherapy with excipient-free rhein/DOX nanodispersions

“…The force field parameters for DOX and RHE molecules were obtained from the generalized Amber force field (GAFF). The atomic charges were generated with the restrained electrostatic potential (RESP) method [33,34]. An artificial box containing 8 DOX, 8 RHE and 2000 water molecules was generated by using the leap module in Amber Tools.…”