Congo Red as a Supramolecular Carrier System for Doxorubicin: An Approach to Understanding the Mechanism of Action

Kwiecińska, Klaudia; Stachowicz‐Kuśnierz, Anna; Korchowiec, Beata; Roman, Maciej; Kwiatek, Wojciech M.; Jagusiak, Anna; Roterman, Irena; Korchowiec, Jacek

doi:10.3390/ijms23168935

Cited by 4 publications

(8 citation statements)

References 44 publications

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“…This observation points towards a conclusion that the membrane has to be in a relaxed state in order for CR entry to occur. This is in agreement with our previous simulations with ordered DPPC membranes [35], where spontaneous entry was not observed. MD simulations show that the affinity of CR towards the membrane is rooted in the cooperation of electrostatic and van der Waals forces.…”

Section: Discussionsupporting

confidence: 94%

“…In this respect, the active role of CR in promoting the transfer of doxorubicin through the headgroups region is an important finding. In our previous study, where DPPC membranes were used, we concluded that the main role of CR in promoting DOX uptake by MCF7 cells lies in the change in the aggregation patterns of DOX in water [ 35 ], namely, in the presence of CR, the bioavailability of DOX was increased by incorporating DOX molecules into the DOX + CR clusters and increasing the drug’s solubility. Spontaneous penetration of the DPPC membrane by either CR or DOX + CR clusters was not observed in that study.…”

Section: Discussionmentioning

confidence: 99%

“…It is known that DOX molecules enter the cell by passive diffusion [ 1 ]. In one of our previous studies, we have shown that the presence of CR in surrounding medium increases the ability of DOX to penetrate MCF7 breast cancer cells [ 35 ]. With the use of molecular dynamics (MD) methods, we have shown that, by incorporating neutral DOX molecules in supramolecular aggregates, CR precludes the precipitation of DOX, which by itself has a low solubility in water [ 36 ].…”

Section: Introductionmentioning

confidence: 99%

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

Stachowicz-Kuśnierz,

Rychlik,

Korchowiec

et al. 2024

Molecules

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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.

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Section: Discussionsupporting

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Stachowicz-Kuśnierz,

Rychlik,

Korchowiec

et al. 2024

Molecules

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“…Previous studies have shown that both compounds have the ability to penetrate cells [ 35 , 53 ] and cause changes in signaling pathways. Our study demonstrated that treatment of RT4 and T24 bladder cancer cells with sorafenib or CR-BAY 5:1 reduced Akt and Erk phosphorylation, which may be closely related to the decrease in proliferation and induction of apoptosis we observed.…”

Section: Discussionmentioning

confidence: 99%

“…This compound is known as a dye, e.g., in the diagnosis of amyloidosis. However, its supramolecular structure and the ability to react with anti-cancer compounds is undoubtedly an innovative approach in targeted therapy [ 34 , 35 ]. Studies show that well-known colloidal drug aggregators (including sorafenib) can be co-formulated with bis-azo dyes to form colloids that are much more stable and much more monodisperse than colloidal aggregates.…”

Section: Introductionmentioning

confidence: 99%

The Potential of Congo Red Supplied Aggregates of Multitargeted Tyrosine Kinase Inhibitor (Sorafenib, BAY-43-9006) in Enhancing Therapeutic Impact on Bladder Cancer

Lasota,

Jankowski,

Wiśniewska

et al. 2023

IJMS

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Bladder cancer is a common malignancy associated with high recurrence rates and potential progression to invasive forms. Sorafenib, a multi-targeted tyrosine kinase inhibitor, has shown promise in anti-cancer therapy, but its cytotoxicity to normal cells and aggregation in solution limits its clinical application. To address these challenges, we investigated the formation of supramolecular aggregates of sorafenib with Congo red (CR), a bis-azo dye known for its supramolecular interaction. We analyzed different mole ratios of CR-sorafenib aggregates and evaluated their effects on bladder cancer cells of varying levels of malignancy. In addition, we also evaluated the effect of the test compounds on normal uroepithelial cells. Our results demonstrated that sorafenib inhibits the proliferation of bladder cancer cells and induces apoptosis in a dose-dependent manner. However, high concentrations of sorafenib also showed cytotoxicity to normal uroepithelial cells. In contrast, the CR-BAY aggregates exhibited reduced cytotoxicity to normal cells while maintaining anti-cancer activity. The aggregates inhibited cancer cell migration and invasion, suggesting their potential for metastasis prevention. Dynamic light scattering and UV-VIS measurements confirmed the formation of stable co-aggregates with distinctive spectral properties. These CR-sorafenib aggregates may provide a promising approach to targeted therapy with reduced cytotoxicity and improved stability for drug delivery in bladder cancer treatment. This work shows that the drug-excipient aggregates proposed and described so far, as Congo red—sorafenib, can be a real step forward in anti-cancer therapies.

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Research progress in tumor therapy of carrier-free nanodrug

An,

Zhang,

Zhang

et al. 2024

Biomedicine & Pharmacotherapy

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Congo Red as a Supramolecular Carrier System for Doxorubicin: An Approach to Understanding the Mechanism of Action

Cited by 4 publications

References 44 publications

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

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

The Potential of Congo Red Supplied Aggregates of Multitargeted Tyrosine Kinase Inhibitor (Sorafenib, BAY-43-9006) in Enhancing Therapeutic Impact on Bladder Cancer

Research progress in tumor therapy of carrier-free nanodrug

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