DFT and Molecular Docking Study of HA-Conjugated SWCNTs for CD44-Targeted Delivery of Platinum-Based Chemotherapeutics
<b>Background:</b> Hyaluronicacid (HA)-conjugated nanocarriers leverage CD44 receptor overexpression on tumor cells for targeted delivery of platinum chemotherapeutics. <b>Methods:</b> This study compares non-functionalized (DDS1) versus HA-conjugated single-walled carbon nan...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-05-01
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| Series: | Pharmaceuticals |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1424-8247/18/6/805 |
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| Summary: | <b>Background:</b> Hyaluronicacid (HA)-conjugated nanocarriers leverage CD44 receptor overexpression on tumor cells for targeted delivery of platinum chemotherapeutics. <b>Methods:</b> 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). <b>Results:</b> 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 (<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mo>Δ</mo></semantics></math></inline-formula>Score ≈ −65 kcal mol<sup>−1</sup>). <b>Conclusions:</b> These results motivate experimental follow-up to confirm whether DDS2 can translate the in silico affinity gains into improved targeted delivery of platinum chemotherapeutics. |
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| ISSN: | 1424-8247 |