Department of Materials Science and Technology, University of Crete, Voutes Campus Greece, Crete, Greece.
Institute of Electronic Structure and Laser/Foundation for Research and Technology-Hellas, (FORTH), Nikolaou Plastira 100, Vassilika Vouton, Heraklion, Crete, Greece.
Soft Matter. 2023 Nov 22;19(45):8684-8697. doi: 10.1039/d3sm00930k.
The investigation of potential self-assembled peptides as carriers for the delivery of anticancer drug Bortezomib is the topic of the present study. The self-assembly of Bortezomib in water is examined using all-atom molecular dynamics simulations and corresponding experimental results from FESEM experiments. In addition, a series of dipeptides with a similar chemical formula to Bortezomib with hydrogel-forming ability are being investigated for their propensity to bind to the drug molecule. Dipeptides are divided into two classes, the protected FF (Fmoc-FF and Z-FF) and the LF-based (Cyclo-LF and LF) ones. The thermodynamic stability of the complexes formed in an aqueous environment, as well as key morphological features of the nanoassemblies are investigated at the molecular level. Binding enthalpy between Bortezomib and dipeptides follows the increasing order: LF < Cyclo-LF < Fmoc-FF < Z-FF under both van der Waals and electrostatic contributions. Protected FF dipeptides have a higher affinity for the drug molecule, which will favor its entrapment, giving them an edge over the LF based dipeptides. By evaluating the various measures, regarding both the binding between the two components and the eventual ability of controlled drug release, we conclude that the protected FF class is a more suitable candidate for drug release of Bortezomib, whereas among its two members, Fmoc-FF appears to be more promising. The selection of the optimal candidates based on the present computational study will be a stepping stone for future detailed experimental studies involving the encapsulation and controlled release of Bortezomib both and .
本研究探讨了潜在的自组装肽作为抗癌药物硼替佐米载体的应用。采用全原子分子动力学模拟和 FESEM 实验的相应实验结果研究了硼替佐米在水中的自组装情况。此外，还研究了一系列具有与硼替佐米相似化学结构且具有水凝胶形成能力的二肽，以研究它们与药物分子结合的倾向。二肽分为两类，即具有保护基的 FF（Fmoc-FF 和 Z-FF）和基于 LF 的（Cyclo-LF 和 LF）。在水相环境中，研究了复合物的热力学稳定性以及纳米组装体的关键形态特征。在范德华力和静电贡献的共同作用下，硼替佐米与二肽形成的复合物的结合焓遵循以下顺序：LF <Cyclo-LF <Fmoc-FF <Z-FF。保护基 FF 二肽与药物分子的亲和力更高，这将有利于其包埋，使其优于基于 LF 的二肽。通过评估各种措施，包括两个组分之间的结合以及最终控制药物释放的能力，我们得出结论，保护基 FF 类是硼替佐米药物释放更合适的候选物，而在其两个成员中，Fmoc-FF 似乎更有前途。基于本计算研究选择最佳候选物将为未来涉及硼替佐米的封装和控制释放的详细实验研究奠定基础。
