In the search for alternative photosensitizers for use in photodynamic therapy (PDT), herein we describe two new water-soluble porphyrins, a neutral fourfold-symmetric compound and a +3-charged tris-methylpyridinium derivative, in which either four or one [1,4,7]-triazacyclononane (TACN) units are connected to the porphyrin macrocycle through a hydrophilic linker; we also report their corresponding tetracationic Re(I) conjugates. The in vitro (photo)toxic effects of the compounds toward the human cell lines HeLa (cervical cancer), H460M2 (non-small-cell lung carcinoma), and HBL-100 (non-tumorigenic epithelial cells) are reported. Three of the compounds are not cytotoxic in the dark up to 100 μM, and the fourfold-symmetric couple revealed very good phototoxic indexes (PIs). The intracellular localization of all derivatives was studied in HeLa cells by confocal fluorescence microscopy. Although low nuclear localization was observed for some of them, it still prompted us to investigate their capacity to bind both quadruplex and duplex DNA; we observed significant selectivity in the tris-methylpyridinium derivatives for G-quadruplex interactions.

Phototoxic Activity and DNA Interactions of Water-Soluble Porphyrins and Their Rhenium(I) Conjugates

MION, GIULIANA;GIANFERRARA, TERESA;BERGAMO, ALBERTA;ALESSIO, ENZO
2015-01-01

Abstract

In the search for alternative photosensitizers for use in photodynamic therapy (PDT), herein we describe two new water-soluble porphyrins, a neutral fourfold-symmetric compound and a +3-charged tris-methylpyridinium derivative, in which either four or one [1,4,7]-triazacyclononane (TACN) units are connected to the porphyrin macrocycle through a hydrophilic linker; we also report their corresponding tetracationic Re(I) conjugates. The in vitro (photo)toxic effects of the compounds toward the human cell lines HeLa (cervical cancer), H460M2 (non-small-cell lung carcinoma), and HBL-100 (non-tumorigenic epithelial cells) are reported. Three of the compounds are not cytotoxic in the dark up to 100 μM, and the fourfold-symmetric couple revealed very good phototoxic indexes (PIs). The intracellular localization of all derivatives was studied in HeLa cells by confocal fluorescence microscopy. Although low nuclear localization was observed for some of them, it still prompted us to investigate their capacity to bind both quadruplex and duplex DNA; we observed significant selectivity in the tris-methylpyridinium derivatives for G-quadruplex interactions.
2015
Pubblicato
File in questo prodotto:
File Dimensione Formato  
cmdc.201500288.pdf

Accesso chiuso

Tipologia: Documento in Versione Editoriale
Licenza: Copyright Editore
Dimensione 2.18 MB
Formato Adobe PDF
2.18 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
2848618_cmdc.201500288-PostPrint.pdf

accesso aperto

Descrizione: Post Print VQR3
Tipologia: Bozza finale post-referaggio (post-print)
Licenza: Digital Rights Management non definito
Dimensione 2.77 MB
Formato Adobe PDF
2.77 MB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11368/2848618
Citazioni
  • ???jsp.display-item.citation.pmc??? 8
  • Scopus 34
  • ???jsp.display-item.citation.isi??? 33
social impact