Khan Muhammad Uzair, Jabeen Ishrat, Althagafi Abdulhamid, Farooq Muhammad Umar, Harb Moussab, Arkook Bassim
School of Interdisciplinary Engineering and Sciences, National University of Sciences and Technology, Islamabad 44000, Pakistan.
Pharmacy Practice Department, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
Pharmaceuticals (Basel). 2025 May 27;18(6):805. doi: 10.3390/ph18060805.
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.
透明质酸（HA）共轭纳米载体利用肿瘤细胞上CD44受体的过表达来实现铂类化疗药物的靶向递送。本研究比较了非功能化的（DDS1）与HA共轭的单壁碳纳米管（DDS2）对顺铂、卡铂和洛铂的包封稳定性及与CD44的结合情况。密度泛函理论计算采用PBE - GGA，结合Tkatchenko - Scheffler色散校正和ZORA相对论处理方法，DDS1使用有限（8,8）扶手椅型单壁碳纳米管（24.6 Å，氢封端），DDS2使用EDC/NHS偶联的HA低聚物。我们计算了结合能、HOMO - LUMO能隙、分子静电势和能量分解。与CD44（PDB ID：4PZ3）的分子对接使用Molegro Virtual Docker，并通过对天然HA片段重新对接（RMSD 1.79 Å）进行验证。DDS2与DDS1的DFT结合能（eV）分别为-7.92 / -7.48（顺铂）、-8.93 / -8.30（卡铂）和-9.72 / -9.25（洛铂），表明HA功能化增强了稳定性。能量分解显示DDS2的范德华力增加约0.4 eV，静电力增加约0.2 eV。分子静电势图证实DDS2上有额外的负电位区域，与药物的正电位位点互补。分子对接得到DDS2的MolDock评分为-171.26，而DDS1为-106.68，反映出更强的CD44亲和力。对接分数表明HA共轭显著增强了碳纳米管载体对CD44受体的预测亲和力（ΔScore≈-65 kcal mol）。这些结果促使进行实验后续研究，以确认DDS2是否能将计算机模拟的亲和力提升转化为铂类化疗药物靶向递送的改善。
