title: A bimodal fluorescent and photocytotoxic naphthalene diimide for theranostic applications.
abstract: We report on the potential of a water-soluble tetracationic quaternary ammonium naphthalene diimide (NDI) as multifunctional agent of interest for theranostic applications. The DNA binding ability of this NDI has been investigated. NDI exhibits high binding constants for G-quadruplex DNA but it is not selective for this type of DNA. Taking advantage of its intrinsic fluorescence and singlet oxygen sensitizing ability, cellular uptake, cytotoxicity and photocytotoxicity have been investigated. The intense emission in the red/NIR allows monitoring of the cell permeability of this charged tetracationic NDI, accumulating into the cell nuclei. No dark cytotoxicity has been observed on selected tumor cell lines. Irradiation of the NDI loaded cells with red light reduces cell viability up to 40% and causes a significant increase of the percentage of cells expressing γH2AX foci indicating DNA damage. The presence of distinct DNA damage foci inside the nucleus suggests that the NDI molecule might induce DNA damage in specific sites. To the best of our knowledge this is the first NDI exhibiting PDT activity at μM concentration combined with low dark cytotoxicity.
authors.affiliation: Oncogenomic and Epigenetic Unit, Regina Elena National Cancer Institute, Via Elio Chianesi, 53 Rome, Italy.
authors.forename: Erica
authors.initials: E
authors.lastname: Salvati
authors.affiliation: Dipartimento di Chimica, Università di Pavia, V.le Taramelli 10, 27100 Pavia, Italy. mauro.freccero@unipv.it.
authors.forename: Filippo
authors.initials: F
authors.lastname: Doria
authors.affiliation: Istituto per la Sintesi Organica e la Fotoreattività, Consiglio Nazionale delle Ricerche, via Gobetti 101, 40129 Bologna, Italy. ilse.manet@isof.cnr.it.
authors.forename: Francesco
authors.initials: F
authors.lastname: Manoli
authors.affiliation: Oncogenomic and Epigenetic Unit, Regina Elena National Cancer Institute, Via Elio Chianesi, 53 Rome, Italy.
authors.forename: Carmen
authors.initials: C
authors.lastname: D'Angelo
authors.affiliation: Oncogenomic and Epigenetic Unit, Regina Elena National Cancer Institute, Via Elio Chianesi, 53 Rome, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Biroccio
authors.affiliation: Dipartimento di Chimica, Università di Pavia, V.le Taramelli 10, 27100 Pavia, Italy. mauro.freccero@unipv.it.
authors.forename: Mauro
authors.initials: M
authors.lastname: Freccero
authors.affiliation: Istituto per la Sintesi Organica e la Fotoreattività, Consiglio Nazionale delle Ricerche, via Gobetti 101, 40129 Bologna, Italy. ilse.manet@isof.cnr.it.
authors.forename: Ilse
authors.initials: I
authors.lastname: Manet
mesh_terms: D001692:Biological Transport; D045744:Cell Line, Tumor; D002470:Cell Survival; D004055:Differential Thermal Analysis / Q000379:methods; D005456:Fluorescent Dyes / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity*; D054856:G-Quadruplexes; D006801:Humans; D007094:Imides / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity*; D015394:Molecular Structure; D009281:Naphthalenes / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity*; D061848:Optical Imaging; D055668:Photochemical Processes; D026082:Singlet Oxygen / Q000737:chemistry; D013329:Structure-Activity Relationship; D000068936:Theranostic Nanomedicine / Q000379:methods*; D013816:Thermodynamics
chemical_list: D005456:Fluorescent Dyes; D007094:Imides; D009281:Naphthalenes; D026082:Singlet Oxygen; C542131:naphthalenediimide