Dendrimer platforms for targeted doxorubicin delivery : physicochemical properties in context of biological responses

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Szota, Magdalena and Szwedowicz, Urszula and Rembialkowska, Nina and Janicka-Klos, Anna and Doveiko, Daniel and Chen, Yu and Kulbacka, Julita and Jachimska, Barbara (2024) Dendrimer platforms for targeted doxorubicin delivery : physicochemical properties in context of biological responses. International Journal of Molecular Sciences, 25 (13). 7201. ISSN 1422-0067 (https://doi.org/10.3390/ijms25137201)

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Abstract

The unique structure of G4.0 PAMAM dendrimers allows a drug to be enclosed in internal spaces or immobilized on the surface. In the conducted research, the conditions for the formation of the active G4.0 PAMAM complex with doxorubicin hydrochloride (DOX) were optimized. The physicochemical properties of the system were monitored using dynamic light scattering (DLS), circular dichroism (CD), and fluorescence spectroscopy. The Quartz Crystal Microbalance with Dissipation Monitoring (QCM-D) method was chosen to determine the preferential conditions for the complex formation. The highest binding efficiency of the drug to the cationic dendrimer was observed under basic conditions when the DOX molecule was deprotonated. The decrease in the zeta potential of the complex confirms that DOX immobilizes through electrostatic interaction with the carrier’s surface amine groups. The binding constants were determined from the fluorescence quenching of the DOX molecule in the presence of G4.0 PAMAM. The two-fold way of binding doxorubicin in the structure of dendrimers was visible in the Isothermal calorimetry (ITC) isotherm. Fluorescence spectra and release curves identified the reversible binding of DOX to the nanocarrier. Among the selected cancer cells, the most promising anticancer activity of the G4.0-DOX complex was observed in A375 malignant melanoma cells. Moreover, the preferred intracellular location of the complexes concerning the free drug was found, which is essential from a therapeutic point of view.

ORCID iDs

Szota, Magdalena, Szwedowicz, Urszula, Rembialkowska, Nina, Janicka-Klos, Anna, Doveiko, Daniel ORCID logoORCID: https://orcid.org/0000-0002-0516-689X, Chen, Yu, Kulbacka, Julita and Jachimska, Barbara;
CORE (COnnecting REpositories)