Title
Cytotoxicity of doxorubicin conjugated with C60 fullerene. Structural and in vitro studies
Author
Kamila Butowska, Witold Kozak, Magdalena Zdrowowicz, Samanta Makurat, Michał Rychłowski, Aleksandra Hać, Anna Herman-Antosiewicz, Jacek Piosik, Janusz Rak
Year
2019
Journal
Structural Chemistry
Abstract
Conjugating an anticancer drug of high biological efficacy but large cytotoxicity with a “transporting” molecule of low toxicity constitutes a valuable approach to design safe drug delivery system. In the present study, doxorubicin (DOX) a drug of large cardiotoxicity was chemically conjugated to a C60-fullerene. The synthesized molecule, a fullerene-doxorubicin conjugate (Ful-DOX), was characterized using the 1H NMR and MALDI TOF mass spectrometry. The absorption and fluorescence spectra and dynamic light scattering of the conjugate were recorded in an aqueous solution, while the impact on viability of several cancer cell lines of the free DOX and the conjugate was compared using the SRB and WST-1 assays. A low antiproliferative activity of the conjugate as compared to the free DOX is a consequence of the presence of fullerene moiety in the former, which is also responsible for the conjugate aggregation in an aqueous solution. Unlike free DOX, these aggregates cannot pass through the nuclear membrane (as demonstrated by the confocal microscopy measurements), which makes them marginally cytotoxic.
Instrument
FP-8500
Keywords
Fluorescence, Aggregation, Chemical stability, Biochemistry, Medicinal