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

doi:10.3390/molecules21020194

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 journal › Article › Research › peer-review

11 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 language	English
Article number	194
Pages (from-to)	1-16
Number of pages	16
Journal	Molecules
Volume	21
Issue number	2
DOIs	https://doi.org/10.3390/molecules21020194
Publication status	Published - 1 Feb 2016

Keywords

Cell-penetrating peptide
Fluorescence
Gadolinium complex
Photo-cytotoxicity
Theranostic

Access to Document

10.3390/molecules21020194

Cite this

@article{6754b0012ffa4e2886697bc7732dade8,

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.",

keywords = "Cell-penetrating peptide, Fluorescence, Gadolinium complex, Photo-cytotoxicity, Theranostic",

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

year = "2016",

month = feb,

day = "1",

doi = "10.3390/molecules21020194",

language = "English",

volume = "21",

pages = "1--16",

journal = "Molecules",

issn = "1420-3049",

publisher = "MDPI AG",

number = "2",

}

TY - JOUR

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

AU - Graham, Bimbil

PY - 2016/2/1

Y1 - 2016/2/1

N2 - 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.

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.

KW - Cell-penetrating peptide

KW - Fluorescence

KW - Gadolinium complex

KW - Photo-cytotoxicity

KW - Theranostic

UR - http://www.scopus.com/inward/record.url?scp=84963692212&partnerID=8YFLogxK

UR - http://www.mdpi.com/1420-3049/21/2/194

U2 - 10.3390/molecules21020194

DO - 10.3390/molecules21020194

M3 - Article

AN - SCOPUS:84963692212

SN - 1420-3049

VL - 21

SP - 1

EP - 16

JO - Molecules

JF - Molecules

IS - 2

M1 - 194

ER -

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

Abstract

Keywords

Access to Document

Other files and links

Tags and algorithms for studies of protein structures and interactions

Expanding the molecular tool set for structural studies of proteins and their complexes

Functionalized Nanomaterials for Application as Multimodal Cancer Imaging Agents

Cite this

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

Abstract

Keywords

Access to Document

Other files and links

Projects

Tags and algorithms for studies of protein structures and interactions

Expanding the molecular tool set for structural studies of proteins and their complexes

Functionalized Nanomaterials for Application as Multimodal Cancer Imaging Agents

Cite this