Polymer-Modified Carbon Nanotubes as Smart Carriers for Anticancer Drug Delivery: Insights from MD and DFT Calculations

Carbon nanotubes (CNTs) have emerged as promising nanocarriers in targeted drug delivery, leveraging their unique physicochemical properties. Polymer modification of single-walled carbon nanotubes (SWCNTs) enhances their solubility and biocompatibility, improving the delivery of anticancer drugs such as thalidomide (Thal), 5-fluorouracil (5-FU), and Temozolomide (TMZ) to target cells. In this context, hybridization refers to the noncovalent interactions between the polyfluorene binop (PFOB) polymer and the CNT surface, enhancing drug adsorption properties. Additionally, quantum theory of atoms in molecules (QTAIM) calculations are utilized to examine the interactions between anticancer drugs and their carriers. The results confirm that the pharmaceutical adsorption process on the carrier complexes is stable, with noncovalent polymer interactions playing a key role. The PFOB modification of CNTs significantly enhances the interaction energies between the drugs and the CNT surface. The interaction energies are approximately -326.26 kJ/mol for Thal/CNT-PFOB compared to -234.98 kJ/mol for Thal/CNT, -305.67 kJ/mol for TMZ/CNT-PFOB versus -261.35 kJ/mol for TMZ/CNT, and -266.91 kJ/mol for 5-FU/CNT-PFOB compared to -92.06 kJ/mol for 5-FU/CNT. PFOB, a conjugated polymer, was noncovalently coated on CNT surfaces to improve drug adsorption. The PFOB layer introduces additional π-π stacking, hydrophobic, and hydrogen bonding sites, significantly enhancing the interaction energies between CNTs and anticancer drugs. This enhancement depends on the structural compatibility between the drug and the polymer-coated surface. Moreover, the effect of temperature on drug adsorption was investigated at 310, 330, and 350 K. The results revealed that the adsorption of pharmaceutical molecules on CNT and CNT-PFOB surfaces increases with rising temperature. Additionally, under acidic conditions, drug protonation weakens interactions with both CNT and CNT-PFOB nanocarriers, enabling drug release.Metadynamics simulations further demonstrate free energy minima for stable complexes, with values around -347.46 kJ/mol for TMZ/CNT and -536.73 kJ/mol for Thal/CNT-PFOB. These results underscore the potential of CNTs and PFOB-modified CNTs, which are modified through noncovalent interactions, as effective nanocarriers for enhanced drug delivery. They offer high loading capacities and improved stability in aqueous environments. Furthermore, we provide guidelines for optimizing CNT-PFOB-based drug delivery strategies.