Amphiphilicity-Controlled Localization of Red Emitting Bicationic Fluorophores in Tumor Cells Acting as Bio-Probes and Anticancer Drugs
Alessio Cesaretti,
Letizia Mencaroni,
Carmela Bonaccorso,
Valentina Botti,
Eleonora Calzoni,
Benedetta Carlotti,
Cosimo Gianluca Fortuna,
Nicolò Montegiove,
Anna Spalletti,
Fausto Elisei
Affiliations
Alessio Cesaretti
Department of Chemistry, Biology and Biotechnology and “Centro di Eccellenza Materiali Innovativi Nanostrutturati” (CEMIN), University of Perugia, Via Elce di Sotto 8, 06123 Perugia, Italy
Letizia Mencaroni
Department of Chemistry, Biology and Biotechnology and “Centro di Eccellenza Materiali Innovativi Nanostrutturati” (CEMIN), University of Perugia, Via Elce di Sotto 8, 06123 Perugia, Italy
Carmela Bonaccorso
Department of Chemical Sciences, University of Catania, Viale Andrea Doria 6, 95125 Catania, Italy
Valentina Botti
Department of Chemistry, Biology and Biotechnology and “Centro di Eccellenza Materiali Innovativi Nanostrutturati” (CEMIN), University of Perugia, Via Elce di Sotto 8, 06123 Perugia, Italy
Eleonora Calzoni
Department of Chemistry, Biology and Biotechnology and “Centro di Eccellenza Materiali Innovativi Nanostrutturati” (CEMIN), University of Perugia, Via Elce di Sotto 8, 06123 Perugia, Italy
Benedetta Carlotti
Department of Chemistry, Biology and Biotechnology and “Centro di Eccellenza Materiali Innovativi Nanostrutturati” (CEMIN), University of Perugia, Via Elce di Sotto 8, 06123 Perugia, Italy
Cosimo Gianluca Fortuna
Department of Chemical Sciences, University of Catania, Viale Andrea Doria 6, 95125 Catania, Italy
Nicolò Montegiove
Department of Chemistry, Biology and Biotechnology and “Centro di Eccellenza Materiali Innovativi Nanostrutturati” (CEMIN), University of Perugia, Via Elce di Sotto 8, 06123 Perugia, Italy
Anna Spalletti
Department of Chemistry, Biology and Biotechnology and “Centro di Eccellenza Materiali Innovativi Nanostrutturati” (CEMIN), University of Perugia, Via Elce di Sotto 8, 06123 Perugia, Italy
Fausto Elisei
Department of Chemistry, Biology and Biotechnology and “Centro di Eccellenza Materiali Innovativi Nanostrutturati” (CEMIN), University of Perugia, Via Elce di Sotto 8, 06123 Perugia, Italy
Small organic molecules arouse lively interest for their plethora of possible biological applications, such as anticancer therapy, for their ability to interact with nucleic acids, or bioimaging, thanks to their fluorescence emission. Here, a panchromatic series of styryl-azinium bicationic dyes, which have already proved to exhibit high water-solubility and significant red fluorescence in water, were investigated through spectrofluorimetric titrations to assess the extent of their association constants with DNA and RNA. Femtosecond-resolved transient absorption spectroscopy was also employed to characterize the changes in the photophysical properties of these fluorophores upon interaction with their biological targets. Finally, in vitro experiments conducted on tumor cell lines revealed that some of the bicationic fluorophores had a peculiar localization within cell nuclei exerting important antiproliferative effects, others were instead found to localize in the cytoplasm without leading to cell death, being useful to mark specific organelles in light of live cell bioimaging. Interestingly, this molecule-dependent behavior matched the different amphiphilicity featured by these bioactive compounds, which are thus expected to be caught in a tug-of-war between lipophilicity, ensured by the presence of aromatic rings and needed to pass cell membranes, and hydrophilicity, granted by charged groups and necessary for stability in aqueous media.
