DFT and Molecular Docking Study of HA-Conjugated SWCNTs for CD44-Targeted Delivery of Platinum-Based Chemotherapeutics.

Hyaluronicacid (HA)-conjugated nanocarriers leverage CD44 receptor overexpression on tumor cells for targeted delivery of platinum chemotherapeutics. This study compares non-functionalized (DDS1) versus HA-conjugated single-walled carbon nanotubes (DDS2) for encapsulation stability and CD44 binding of Cisplatin, Carboplatin, and Lobaplatin. Density Functional Theory calculations employed PBE-GGA with Tkatchenko-Scheffler dispersion and ZORA relativistic treatment, using a finite (8,8) armchair SWCNT (24.6 Å, H-capped) for DDS1 and an EDC/NHS-coupled HA oligomer for DDS2. We computed binding energies, HOMO-LUMO gaps, Molecular Electrostatic Potentials, and energy decompositions. Molecular docking to CD44 (PDB ID: 4PZ3) used Molegro Virtual Docker, validated by re-docking the native HA fragment (RMSD 1.79 Å). DFT binding energies (eV) for DDS2 versus DDS1 were -7.92/-7.48 (Cisplatin), -8.93/-8.30 (Carboplatin), and -9.72/-9.25 (Lobaplatin), indicating enhanced stabilization by HA functionalization. Energy decomposition showed increases of ∼0.4 eV (vdW) and ∼0.2 eV (electrostatic) in DDS2. MEP maps confirmed additional negative-potential regions on DDS2, complementing drug-positive sites. Molecular docking yielded MolDock scores of -171.26 for DDS2 versus -106.68 for DDS1, reflecting stronger CD44 affinity. Docking scores indicate that HA conjugation notably strengthens the predicted affinity of CNT carriers toward the CD44 receptor (ΔScore ≈ -65 kcal mol). These results motivate experimental follow-up to confirm whether DDS2 can translate the in silico affinity gains into improved targeted delivery of platinum chemotherapeutics.