Gadolinium(III) Porphyrinoid Phototheranostics

Abstract

Molecular phototheranostics as an emerging field of modern precision medicine has recently attracted increasing research attention owing to non-invasiveness, high precision, and controllable nature of light. In this work, we reported promising gadolinium (Gd³⁺ ) porphyrinoids as phototheranostic agents for magnetic resonance imaging (MRI) and photodynamic therapy (PDT). The synthesized Gd-1-4-Glu featured with meso-glycosylation and β-lactonization to endow good biocompatibility and improved photophysical properties. In particular, β-lactonization of glycosylated Gd³⁺ porphyrinoids substantially red-shifted Q band absorption to near-infrared (NIR) region and boosted generation of reactive oxygen species including ¹ O₂ , and some radical species that engaged in both type II and type I PDT pathways. In addition, the number and regioisomerism of β-oxazolone moieties was observed to play an essential role in improving longitude relaxivity (r₁ ) of Gd-1-4-Glu of up to 4.3±0.2 mM^-1 s^-1 by affecting environmental water exchange. Taking Gd-4-Glu as a promising complex, we further achieved real-time T₁ -weighted MRI and PDT on HeLa tumour mice in vivo, revealing the appealing potential of Gd³⁺ porphyrinoids in phototheranostics.

Keywords: Lanthanide chemical biology; MRI; Metalloporphyrinoid; Photodynamic therapy; Phototheranostics.