title: Cellular Uptake and Photo-Cytotoxicity of a Gadolinium(III)-DOTA-Naphthalimide Complex "Clicked" to a Lipidated Tat Peptide.
abstract: A new bifunctional macrocyclic chelator featuring a conjugatable alkynyl-naphthalimide fluorophore pendant group has been prepared and its Gd(III) complex coupled to a cell-penetrating lipidated azido-Tat peptide derivative using Cu(I)-catalysed "click" chemistry. The resulting fluorescent conjugate is able to enter CAL-33 tongue squamous carcinoma cells, as revealed by confocal microscopy, producing a very modest anti-proliferative effect (IC50 = 93 µM). Due to the photo-reactivity of the naphthalimide moiety, however, the conjugate's cytotoxicity is significantly enhanced (IC50 = 16 µM) upon brief low-power UV-A irradiation.
authors: Monash Institute of Pharmaceutical Sciences, Monash University, Parkville VIC 3163, Australia. william.o'malley@monash.edu.
authors: William I
authors: WI
authors: O'Malley
authors: Department of Chemistry, University of Zurich, Winterthurerstrasse 190, Zurich CH-8057, Switzerland. riccardo.rubbiani@chem.uzh.ch.
authors: Riccardo
authors: R
authors: Rubbiani
authors: School of Chemistry, Monash University, Clayton VIC 3800, Australia. margaret.aulsebrook@monash.edu.
authors: Margaret L
authors: ML
authors: Aulsebrook
authors: School of Chemistry, Monash University, Clayton VIC 3800, Australia. mike.grace@monash.edu.
authors: Michael R
authors: MR
authors: Grace
authors: School of Chemistry, Monash University, Clayton VIC 3800, Australia. leone.spiccia@monash.edu.
authors: Leone
authors: L
authors: Spiccia
authors: School of Chemistry, Monash University, Clayton VIC 3800, Australia. kellie.tuck@monash.edu.
authors: Kellie L
authors: KL
authors: Tuck
authors: Department of Chemistry, University of Zurich, Winterthurerstrasse 190, Zurich CH-8057, Switzerland. gilles.gasser@chem.uzh.ch.
authors: Gilles
authors: G
authors: Gasser
authors: Monash Institute of Pharmaceutical Sciences, Monash University, Parkville VIC 3163, Australia. bim.graham@monash.edu.
authors: Bim
authors: B
authors: Graham
mesh_terms: D000970:Antineoplastic Agents / Q000378:metabolism* / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002614:Chelating Agents / Q000378:metabolism / Q000494:pharmacology; D057930:Click Chemistry; D056831:Coordination Complexes / Q000378:metabolism* / Q000494:pharmacology; D005682:Gadolinium / Q000737:chemistry; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry; D006801:Humans; D053644:Naphthalimides / Q000378:metabolism* / Q000494:pharmacology; D017319:Photosensitizing Agents / Q000378:metabolism* / Q000494:pharmacology; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D002614:Chelating Agents; D056831:Coordination Complexes; D006573:Heterocyclic Compounds, 1-Ring; D053644:Naphthalimides; D017319:Photosensitizing Agents; D054322:tat Gene Products, Human Immunodeficiency Virus; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; D005682:Gadolinium
keywords: cell-penetrating peptide; fluorescence; gadolinium complex; photo-cytotoxicity; theranostic