Faculty of Chemistry, Jagiellonian University, Gronostajowa 2, 30-387 Krakow, Poland.
Molecules. 2024 May 30;29(11):2567. doi: 10.3390/molecules29112567.
Doxorubicin (DOX) is a commonly used chemotherapeutic drug, from the anthracycline class, which is genotoxic to neoplastic cells via a DNA intercalation mechanism. It is effective and universal; however, it also causes numerous side effects. The most serious of them are cardiotoxicity and a decrease in the number of myeloid cells. For this reason, targeted DOX delivery systems are desirable, since they would allow lowering the drug dose and therefore limiting systemic side effects. Recently, synthetic dyes, in particular Congo red (CR), have been proposed as possible DOX carriers. CR is a planar molecule, built of a central biphenyl moiety and two substituted naphthalene rings, connected with diazo bonds. In water, it forms elongated ribbon-shaped supramolecular structures, which are able to selectively interact with immune complexes. In our previous studies, we have shown that CR aggregates can intercalate DOX molecules. In this way, they preclude DOX precipitation in water solutions and increase its uptake by MCF7 breast cancer cells. In the present work, we further explore the interactions between DOX, CR, and their aggregates (CR/DOX) with phospholipid membranes. In addition to neutral molecules, the protonated doxorubicin form, DXP, is also studied. Molecular dynamics simulations are employed to study the transfer of CR, DOX, DXP, and their aggregates through POPC bilayers. Interactions of CR, DOX, and CR/DOX with model monolayers are studied with Langmuir trough measurements. This study shows that CR may support the transfer of doxorubicin molecules into the bilayer. Both electrostatic and van der Waals interactions with lipids are important in this respect. The former promote the initial stages of the insertion process, the latter keep guest molecules inside the bilayer.
多柔比星（DOX）是一种常用的化疗药物，属于蒽环类药物，通过 DNA 嵌入机制对肿瘤细胞产生遗传毒性。它是有效且通用的；然而，它也会引起许多副作用。其中最严重的是心脏毒性和骨髓细胞数量减少。因此，靶向 DOX 递送系统是理想的，因为它们可以降低药物剂量，从而限制全身副作用。最近，合成染料，特别是刚果红（CR），已被提议作为可能的 DOX 载体。CR 是一种平面分子，由中央联苯部分和两个取代的萘环组成，通过重氮键连接。在水中，它形成拉长的带状超分子结构，能够选择性地与免疫复合物相互作用。在我们之前的研究中，我们已经表明 CR 聚集物可以嵌入 DOX 分子。这样，它们可以防止 DOX 在水溶液中沉淀，并增加 MCF7 乳腺癌细胞对其的摄取。在本工作中，我们进一步探索了 DOX、CR 及其聚集体（CR/DOX）与磷脂膜之间的相互作用。除了中性分子外，还研究了质子化的多柔比星形式 DXP。采用分子动力学模拟研究了 CR、DOX、DXP 及其聚集体通过 POPC 双层的传递。通过 Langmuir 槽测量研究了 CR、DOX 和 CR/DOX 与模型单层的相互作用。这项研究表明，CR 可能支持多柔比星分子进入双层。在这方面，静电和范德华相互作用都很重要。前者促进插入过程的初始阶段，后者将客体分子保持在双层内。
