Wang Yuhe, Li Junfeng, Li Xuanda, Gao Bingmiao, Chen Jiao, Song Yun
Engineering Research Center of Tropical Medicine Innovation and Transformation of Ministry of Education & International Joint Research Center of Human-Machine Intelligent Collaborative for Tumor Precision Diagnosis and Treatment of Hainan Province & Hainan Provincial Key Laboratory of Research and Development on Tropical Herbs, School of Pharmacy, Hainan Medical University, Haikou, 571199, Hainan, People's Republic of China.
Sci Rep. 2025 Mar 7;15(1):8055. doi: 10.1038/s41598-025-92607-3.
This study investigates the binding interactions between bovine serum albumin (BSA) and camptothecin (CPT) drugs (camptothecin, 10-hydroxycamptothecin, topotecan, and irinotecan) using UV-Vis spectroscopy, fluorescence spectroscopy, three-dimensional fluorescence spectroscopy, and molecular docking techniques. The fluorescence quenching of BSA by CPT drugs follows a static mechanism, with binding constants (K) ranging from 4.23 × 10 M (CPT) to 101.30 × 10 M (irinotecan), demonstrating significant drug binding selectivity. Thermodynamic analysis reveals distinct interaction mechanisms: topotecan binding is driven by hydrogen bonding (ΔH = - 10.96 kJ·mol) and hydrophobic interactions (ΔS = 0.066 kJ·mol·K), while irinotecan exhibits stronger binding dominated by electrostatic forces (ΔH = - 86.77 kJ·mol) with significant entropy loss (ΔS = - 0.161 kJ·mol·K). Molecular docking confirms preferential binding at Sudlow site I of BSA, with hydrophobic interactions and hydrogen bonding as the primary driving forces. These findings provide a comprehensive understanding of CPT-BSA interactions, offering valuable insights for the design of albumin-based drug delivery systems with optimized pharmacokinetic profiles.
本研究采用紫外可见光谱、荧光光谱、三维荧光光谱和分子对接技术，研究了牛血清白蛋白（BSA）与喜树碱（CPT）类药物（喜树碱、10-羟基喜树碱、拓扑替康和伊立替康）之间的结合相互作用。CPT类药物对BSA的荧光猝灭遵循静态机制，结合常数（K）范围为4.23×10⁴ M（CPT）至101.30×10⁴ M（伊立替康），显示出显著的药物结合选择性。热力学分析揭示了不同的相互作用机制：拓扑替康的结合由氢键（ΔH = -10.96 kJ·mol⁻¹）和疏水相互作用（ΔS = 0.066 kJ·mol⁻¹·K⁻¹）驱动，而伊立替康表现出更强的结合，主要由静电力（ΔH = -86.77 kJ·mol⁻¹）主导，伴有显著的熵损失（ΔS = -0.161 kJ·mol⁻¹·K⁻¹）。分子对接证实了在BSA的Sudlow位点I的优先结合，疏水相互作用和氢键为主要驱动力。这些发现为CPT-BSA相互作用提供了全面的理解，为设计具有优化药代动力学特征的基于白蛋白的药物递送系统提供了有价值的见解。
