Synthesis and In Vitro Studies of a Gd(DOTA)–Porphyrin Conjugate for Combined MRI and Photodynamic Treatment

Sébastien Jenni (1) , Celia ́ Bonnet (2) , Frédéric Bolze (3) , Agnes A. Pallier (2) , Angélique Sour (1) , Éva Tóth (2) , Barbara Ventura (4) , Valérie Heitz (1)

1 Institut de Chimie de Strasbourg
2 CBM - Centre de biophysique moléculaire
3 CAMB - Conception et application de molécules bioactives
4 ISOF - Institute of Organic Synthesis and Photoreactivity

With the aim of developing new molecular theranostic agents, a π-extended Zn(II) porphyrin as photosensitizer for photodynamic therapy (PDT) linked to two GdDOTA-type complexes for magnetic resonance imaging (MRI) detection was synthesized. The relaxivity studies revealed a much higher relaxivity value per Gd ion for this medium sized molecule (19.32 mM–1 s–1 at 20 MHz and 298 K) compared to clinical contrast agents—a value which strongly increases in the presence of bovine serum albumin, reaching 25.22 mM–1 s–1. Moreover, the photophysical studies showed the strong ability of the molecule to absorb light in the deep red (670 nm, ε ≈ 60000 M–1 cm–1) and in the near-infrared following two-photon excitation (920 nm, σ2 ≈ 650 GM). The conjugate is also able to generate singlet oxygen, with a quantum yield of 0.58 in DMSO. Promising results were obtained in cellular studies, demonstrating that the conjugate is internalized in HeLa cells at micromolar concentration and leads to 70% of cell death following 30 min irradiation at 660 nm. These results confirm the potential of the designed molecule as an imaging and therapeutic agent.

Domaines: Chimie de coordination; Chimie thérapeutique

Sébastien Jenni, Celia ́ Bonnet, Frédéric Bolze, Agnes A. Pallier, Angélique Sour, et al.. Synthesis and In Vitro Studies of a Gd(DOTA)–Porphyrin Conjugate for Combined MRI and Photodynamic Treatment. Inorganic Chemistry, 2020, 59 (19), pp.14389-14398. ⟨10.1021/acs.inorgchem.0c02189⟩. ⟨hal-03011644⟩