Cytotoxicity of doxorubicin conjugated with C60 fullerene. Structural and in vitro studies

Kamila Butowska , Witold Kozak , Magdalena Zdrowowicz , Samanta Makurat , Michał Rychłowski , Aleksandra Hać , Anna Herman-Antosiewicz , Jacek Piosik , Janusz Rak

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.
Author Kamila Butowska (IFB)
Kamila Butowska ,,
- Intercollegiate Faculty of Biotechnology UG
, Witold Kozak (FCh / DPCh / LBS)
Witold Kozak,,
- Laboratory of Biological Sensitizers
, Magdalena Zdrowowicz (FCh / DPCh / LBS)
Magdalena Zdrowowicz,,
- Laboratory of Biological Sensitizers
, Samanta Makurat (FCh / DPCh / LBS)
Samanta Makurat,,
- Laboratory of Biological Sensitizers
, Michał Rychłowski (IFB / IB / LVMB)
Michał Rychłowski,,
- Laboratory of Virus Molecular Biology
, Aleksandra Hać (FB / DMBG)
Aleksandra Hać,,
- Katedra Biologii i Genetyki Medycznej
, Anna Herman-Antosiewicz (FB / DMBG)
Anna Herman-Antosiewicz,,
- Katedra Biologii i Genetyki Medycznej
, Jacek Piosik (IFB / M020 / DMCB)
Jacek Piosik,,
- Department of Molecular and Cellular Biology
, Janusz Rak (FCh / DPCh / LBS)
Janusz Rak,,
- Laboratory of Biological Sensitizers
Journal seriesStructural Chemistry, ISSN 1040-0400, e-ISSN 1572-9001, (N/A 70 pkt)
Issue year2019
Vol30
No6
Pages2327-2338
Publication size in sheets0.55
Keywords in EnglishFullerene, doxorubicin, covalent conjugate, drug delivery, nanoparticle, cancer cells
ASJC Classification1606 Physical and Theoretical Chemistry; 3104 Condensed Matter Physics
DOIDOI:10.1007/s11224-019-01428-4
URL https://doi.org/10.1007/s11224-019-01428-4
Languageen angielski
LicenseOther; published final; Uznanie Autorstwa (CC-BY); with publication
Score (nominal)70
Score sourcejournalList
ScoreMinisterial score = 70.0, 28-01-2020, ArticleFromJournal
Publication indicators WoS Citations = 0; Scopus SNIP (Source Normalised Impact per Paper): 2017 = 0.525; WoS Impact Factor: 2018 = 1.624 (2) - 2018=1.333 (5)
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