CNR-ISMN c/o Dipartimento di Scienze Chimiche, Biologiche , Farmaceutiche ed Ambientali dell'Università di Messina , Viale F. Stagno d'Alcontres 31 , 98166 , Messina , Italy.
Dipartimento di Biotecnologie e Scienze della Vita (DBSV) , Università dell'Insubria , Via J.H. Dunant 3 , 21100 , Varese , Italy.
Langmuir. 2018 Jul 24;34(29):8639-8651. doi: 10.1021/acs.langmuir.8b01049. Epub 2018 Jul 16.
Amphiphilic cyclodextrins (aCDs) are an intriguing class of carrier systems which, recently, have been proposed to deliver porphyrinoids and anticancer drugs or combined dose of both for dual therapeutic applications. The design of nanoassemblies based on aCD and photosensitizers (PSs) aims to preserve the photodynamic therapy (PDT) efficacy of PS, reducing the tendency of PS to self-aggregate, without affecting the quantum yield of singlet oxygen (O) production, and, not less importantly, minimizing dark toxicity and reducing photosensitization effects. With this idea in mind, in this paper, we focus on nanoassemblies between a non-ionic aCD (SC6OH) and halo-alkyl tailored iodinated boron-dipyrromethenes (BODIPY) dye, a class of molecules which recently have been successfully proposed as a stimulating alternative to porphyrinoids for their high photodynamic efficacy. Nanoassemblies of BODIPY/aCD (BL01I@SC6OH) were prepared in different aqueous media by evaporation of mixed organic film of aCD and BODIPY, hydration, and sonication. The nanostructures were characterized, measuring their hydrodynamic diameter and ξ-potential and also evaluating their time-stability in biological relevant media. Taking advantage of emissive properties of the not-iodinated BODIPY analogue (BL01), nanoassemblies based on aCD and BL01 were investigated as model system to get insight on entanglement of BODIPY in the amphiphile in aqueous dispersion, pointing out that BODIPY is well-entrapped in monomeric form (τ ≅ 6.5 ns) within the colloidal carriers. Also morphology and fluorescence emission properties were elucidated after casting the solution on glass. BL01@SC6OH is easily detectable in cytoplasm of HCT116 cell lines, evidencing the remarkable intracellular penetration of this nanoassembly similar to free BODIPY. On the same cell lines, the photodynamically active assembly BL01I/aCD shows toxicity upon irradiation. Despite the fact that free BL01I is more PDT active than its assembly, aCD can modulate the cell uptake of BODIPY, pointing out the potential of this system for in vivo PDT application.
两亲性环糊精 (aCD) 是一类很有前途的载体系统，最近有人提出将卟啉类药物和抗癌药物或两者的联合剂量用于双重治疗应用。基于 aCD 和光敏剂 (PS) 的纳米组装体的设计旨在保持 PS 的光动力疗法 (PDT) 效果，减少 PS 自聚集的趋势，而不影响单线态氧 (O) 产生的量子产率，而且同样重要的是，最大限度地减少暗毒性并降低光致敏作用。考虑到这一点，在本文中，我们专注于非离子 aCD (SC6OH) 和卤代烷基修饰的碘代硼二吡咯甲川染料 (BODIPY) 之间的纳米组装体，BODIPY 是一类分子，最近已成功提出作为卟啉类药物的刺激替代物，因其具有高的光动力疗效。BODIPY/aCD (BL01I@SC6OH) 纳米组装体通过蒸发混合 aCD 和 BODIPY 的有机膜、水合和超声在不同的水介质中制备。通过测量水动力学直径和 ξ-电位以及评估它们在生物相关介质中的时稳定性来表征纳米结构。利用未碘化 BODIPY 类似物 (BL01) 的发射性质，研究了基于 aCD 和 BL01 的纳米组装体作为模型系统，以深入了解 BODIPY 在水分散体中与两亲物的缠结，指出 BODIPY 很好地以单体形式 (τ ≅ 6.5 ns) 被包埋在胶体载体中。还阐明了溶液在玻璃上浇铸后的形态和荧光发射性质。BL01@SC6OH 很容易在 HCT116 细胞系的细胞质中检测到，这表明这种纳米组装体具有类似于游离 BODIPY 的显著细胞内穿透性。在相同的细胞系中，具有光动力活性的组装体 BL01I/aCD 在照射下显示出毒性。尽管游离 BL01I 比其组装体具有更高的 PDT 活性，但 aCD 可以调节 BODIPY 的细胞摄取，这表明该系统具有用于体内 PDT 应用的潜力。
