Silicon Phthalocyanines Functionalized with Axial Substituents Targeting PSMA: Synthesis and Preliminary Assessment of Their Potential for PhotoDynamic Therapy of Prostate Cancer

Photodynamic therapy (PDT) is a clinical modality based on the irradiation of different diseases, mostly tumours, with light following the selective uptake of a photosensitiser by the pathological tissue. In this study, two new silicon(IV)phtalocyanines (SiPcs) functionalized at both axial positions with a PSMA inhibitor are reported as candidate photosensitizers for PDT of prostate cancer, namely compounds SiPc-PQ(PSMAi)₂ and SiPc-OSi(PSMAi)₂. These compounds share the same PSMA-binding motif, but differ in the linker that connects the inhibitor moiety to the Si(IV) atom: an alkoxy (Si−O−C) bond for SiPc-PQ(PSMAi)₂, and a silyloxy (Si−O−Si) bond for SiPc-OSi(PSMAi)₂. Both compounds were synthesized by a facile synthetic route and fully characterized by 2D NMR, mass spectrometry and absorption/fluorescence spectrophotometry. The PDT agents showed a suitable solubility in water, where they essentially exist in monomeric form. SiPc-PQ(PSMAi)₂ showed a higher singlet oxygen quantum yield Φ_Δ, higher fluorescence quantum yields Φ_F and better photostability than SiPc-OSi(PSMAi)₂. Both compounds were efficiently taken up by PSMA(+) PC3-PIP cells, but not by PSMA(−) PC3-FLU cells. However, SiPc-PQ(PSMAi)₂ showed a more specific photoinduced cytotoxicity in vitro, which is likely attributable to a better stability of its water solutions.