Insights into Transfer of Supramolecular Doxorubicin/Congo Red Aggregates through Phospholipid Membranes

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...

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Published in:	Molecules (Basel, Switzerland) Vol. 29; no. 11; p. 2567
Main Authors:	Stachowicz-Kuśnierz, Anna, Rychlik, Paulina, Korchowiec, Jacek, Korchowiec, Beata
Format:	Journal Article
Language:	English
Published:	Switzerland MDPI AG 30-05-2024 MDPI
Subjects:	Adsorption Anthracyclines biomembranes Cancer Congo red Congo Red - chemistry doxorubicin Doxorubicin - chemistry Doxorubicin - pharmacology Drug Carriers - chemistry drug delivery Genetic aspects Humans Langmuir trough experiments Lipid Bilayers - chemistry Lipids MCF-7 Cells Molecular dynamics Molecular Dynamics Simulation molecular dynamics simulations Phospholipids Phospholipids - chemistry Simulation Simulation methods Toxicity molecular dynamics simulations Langmuir trough experiments Congo red doxorubicin drug delivery biomembranes
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1420-3049 1420-3049
DOI:	10.3390/molecules29112567