Four Gadolinium(III) Complexes Appended to a Porphyrin: A Water-Soluble Molecular Theranostic Agent with Remarkable Relaxivity Suited for MRI Tracking of the Photosensitizer

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• 作者：Angélique Sour ; Sébastien Jenni ; Ana Ortí-Suárez ; Julie Schmitt ; Valérie Heitz ; Frédéric Bolze ; Paulo Loureiro de Sousa ; Chrystelle Po ; Célia S. Bonnet ; Agnès Pallier ; Éva Tóth ; Barbara Ventura
• 刊名：Inorganic Chemistry
• 出版年：2016
• 出版时间：May 2, 2016
• 年：2016
• 卷：55
• 期：9
• 页码：4545-4554
• 全文大小：527K
• 年卷期：0
• ISSN：1520-510X

文摘

A molecular theranostic agent for magnetic resonance imaging (MRI) and photodynamic therapy (PDT) consisting of four [GdDTTA]⁻ complexes (DTTA⁴⁻ = diethylenetriamine-N,N,N″,N″-tetraacetate) linked to a meso-tetraphenylporphyrin core, as well as its yttrium(III) analogue, was synthesized. A variety of physicochemical methods were used to characterize the gadolinium(III) conjugate 1 both as an MRI contrast agent and as a photosensitizer. The proton relaxivity measured in H₂O at 20 MHz and 25 °C, r₁ = 43.7 mmol^–1 s^–1 per gadolinium center, is the highest reported for a bishydrated gadolinium(III)-based contrast agent of medium size and can be related to the rigidity of the molecule. The complex displays also a remarkable singlet oxygen quantum yield of ϕ_Δ = 0.45 in H₂O, similar to that of a meso-tetrasulfonated porphyrin. We also evidenced the ability of the gadolinium(III) conjugate to penetrate in cancer cells with low cytotoxicity. Its phototoxicity on Hela cells was evaluated following incubation at low micromolar concentration and moderate light irradiation (21 J cm^–2) induced 50% of cell death. Altogether, these results demonstrate the high potential of this conjugate as a theranostic agent for MRI and PDT.