Department of Chemistry, Lomonosov Moscow State University, 119991 Moscow, Russia.
Department of Medical Nanobiotechnology, Pirogov Russian National Research Medical University, 117997 Moscow, Russia.
Molecules. 2021 Dec 7;26(24):7426. doi: 10.3390/molecules26247426.
Imaging-guided delivery is developed for hydrophobic drugs, and to a much lesser extent, hydrophilic ones. In this work we have designed a novel strategy for real-time monitoring of hydrophilic drug delivery. Traditionally, the drug and the dye are covalently attached to a nanocarrier or are electrostatically adsorbed. Recently, we found an efficient way to bind the drug by ion-paring with an appropriate counter-ion to form the aggregate that embeds a hydrophobic dye with a considerable fluorescence enhancement. We synthesized a series of carbocyanine dyes of hydrophobicity sufficient for solubilization in hydrophobic ion pairs, which restores their emission in the near-infrared (NIR) region upon the formation of the ternary aggregates. To avoid using toxic surfactants, we applied an amphiphilic polymer-oligomer poly(hexamethylene guanidine) (PHMG) as a counter-ion. Сeftriaxone was used as a model hydrophilic drug ensuring the highest fluorescent signal. The so-formed drug-counter-ion-dye aggregates were encapsulated into a cross-linked maleated chitosan carrier. Confocal laser scanning microscopy (CLSM) studies have demonstrated internalization of the encapsulated model drug by breast adenocarcinoma cells at 40 min after treatment. These results suggest the potential application of hydrophobic ion pairs containing an NIR dye in imaging-guided delivery of hydrophilic compounds.
在这项工作中，我们设计了一种用于实时监测亲水性药物传递的新策略。传统上，药物和染料通过共价键连接到纳米载体上，或者通过静电吸附连接到纳米载体上。最近，我们发现了一种通过离子配对将药物与适当的抗衡离子结合的有效方法，形成包含疏水性染料的聚集体，具有相当大的荧光增强。我们合成了一系列疏水性足以溶解在疏水性离子对中的碳菁染料，这些染料在形成三元聚集体时会恢复其近红外（NIR）区域的发射。为了避免使用有毒表面活性剂，我们应用了一种两亲性聚合物-低聚物聚（六亚甲基胍）（PHMG）作为抗衡离子。头孢曲松被用作亲水性药物的模型，以确保最高的荧光信号。形成的药物-抗衡离子-染料聚集体被包封在交联马来酸壳聚糖载体中。共聚焦激光扫描显微镜（CLSM）研究表明，在治疗后 40 分钟，乳腺癌细胞内化了包封的模型药物。这些结果表明，含有近红外染料的疏水性离子对在亲水性化合物的成像引导传递中有潜在的应用。
