Cellular uptake and photo-cytotoxicity of a gadolinium(III)-DOTA-naphthalimide complex "clicked" to a lipidated tat peptide

William O'Malley, Riccardo Rubbiani, Maggie Aulsebrook, Michael Grace, Leone Spiccia, Kellie Tuck, Gilles Gasser, Bimbil Graham

Research output: Contribution to journalArticleResearchpeer-review

8 Citations (Scopus)

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.

Original languageEnglish
Article number194
Pages (from-to)1-16
Number of pages16
JournalMolecules
Volume21
Issue number2
DOIs
Publication statusPublished - 1 Feb 2016

Keywords

  • Cell-penetrating peptide
  • Fluorescence
  • Gadolinium complex
  • Photo-cytotoxicity
  • Theranostic

Cite this

O'Malley, William ; Rubbiani, Riccardo ; Aulsebrook, Maggie ; Grace, Michael ; Spiccia, Leone ; Tuck, Kellie ; Gasser, Gilles ; Graham, Bimbil. / Cellular uptake and photo-cytotoxicity of a gadolinium(III)-DOTA-naphthalimide complex "clicked" to a lipidated tat peptide. In: Molecules. 2016 ; Vol. 21, No. 2. pp. 1-16.
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Cellular uptake and photo-cytotoxicity of a gadolinium(III)-DOTA-naphthalimide complex "clicked" to a lipidated tat peptide. / O'Malley, William; Rubbiani, Riccardo; Aulsebrook, Maggie; Grace, Michael; Spiccia, Leone; Tuck, Kellie; Gasser, Gilles; Graham, Bimbil.

In: Molecules, Vol. 21, No. 2, 194, 01.02.2016, p. 1-16.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Cellular uptake and photo-cytotoxicity of a gadolinium(III)-DOTA-naphthalimide complex "clicked" to a lipidated tat peptide

AU - O'Malley, William

AU - Rubbiani, Riccardo

AU - Aulsebrook, Maggie

AU - Grace, Michael

AU - Spiccia, Leone

AU - Tuck, Kellie

AU - Gasser, Gilles

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AB - 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.

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