Barbey Carole, Bouchemal Nadia, Retailleau Pascal, Dupont Nathalie, Spadavecchia Jolanda
CNRS, UMR 7244, NBD-CSPBAT, Laboratoire de Chimie, Structures et Propriétés de Biomatériaux et d'Agents Thérapeutiques Université Sorbonne Paris Nord, 1 Rue de Chablis, Bobigny 93000, France.
CNRS, UPR 2301, Service de Cristallochimie, Institut des Substances Naturelles, 1, Avenue de la Terrasse, Gif sur Yvette 91190, France.
ACS Omega. 2021 Jan 4;6(2):1235-1245. doi: 10.1021/acsomega.0c04501. eCollection 2021 Jan 19.
Idarubicin (IDA) is the analog of daunorubicin (DNR). The absence of the methoxy group at position 4 of IDA remarkably improved lipophilicity, which is responsible for extra cellular uptake, higher DNA-binding ability, and considerable cytotoxicity in correlation with doxorubicin (DOX) and DNR. In this paper, we conceived two principal objectives: we realized the crystal structure of IDA by X-ray diffraction measurements on single crystals at room temperature (monoclinic, space group 2, = 5.1302(2) Å, = 9.9122(5) Å, = 24.8868(11) Å; β = 91.425(4)°; = 1265.14(10) Å) with refinements of the structure converged to the final = 3.87%. The second objective has been to develop gold nanoparticles encapsulated with idarubicin through an original methodology in which gold salt (HAuCl) is chelated with IDA and diacid polymer (PEG) to form hybrid nanoparticles called IDA IN PEG-AuNPs in which drug solubility was enhanced. The computational studies were in agreement with the experimental observations. These hybrid nanoparticles and their precursors were analyzed by Raman, UV-Vis, H NMR, and transmission electron microscopy (TEM). The main results are completed by a theoretical approach to understand the whole process.
伊达比星（IDA）是柔红霉素（DNR）的类似物。IDA第4位上甲氧基的缺失显著提高了亲脂性，这使其具有细胞外摄取能力、更高的DNA结合能力，以及与多柔比星（DOX）和DNR相关的相当大的细胞毒性。在本文中，我们设定了两个主要目标：我们通过在室温下对单晶进行X射线衍射测量实现了IDA的晶体结构（单斜晶系，空间群2，a = 5.1302(2) Å，b = 9.9122(5) Å，c = 24.8868(11) Å；β = 91.425(4)°；V = 1265.14(10) Å），结构精修收敛至最终的R = 3.87%。第二个目标是通过一种原始方法开发包裹有伊达比星的金纳米颗粒，其中金盐（HAuCl）与IDA和二酸聚合物（PEG）螯合形成称为IDA IN PEG-AuNPs的杂化纳米颗粒，药物溶解度在其中得到提高。计算研究与实验观察结果一致。通过拉曼光谱、紫外可见光谱、核磁共振氢谱和透射电子显微镜（TEM）对这些杂化纳米颗粒及其前体进行了分析。主要结果通过理论方法得以完善，以理解整个过程。
