TY - JOUR
T1 - Silicon Phthalocyanines Functionalized with Axial Substituents Targeting PSMA
T2 - Synthesis and Preliminary Assessment of Their Potential for PhotoDynamic Therapy of Prostate Cancer
AU - Capozza, Martina
AU - Digilio, Giuseppe
AU - Gagliardi, Michela
AU - Tei, Lorenzo
AU - Marchesi, Stefano
AU - Terreno, Enzo
AU - Stefania, Rachele
N1 - Publisher Copyright:
© 2024 The Author(s). ChemMedChem published by Wiley-VCH GmbH.
PY - 2024/11/18
Y1 - 2024/11/18
N2 - 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 ΦΔ, higher fluorescence quantum yields ΦF 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.
AB - 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 ΦΔ, higher fluorescence quantum yields ΦF 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.
KW - PSMA
KW - Photodynamic therapy
KW - Prostate cancer
KW - Silicon phthalocyanine
UR - http://www.scopus.com/inward/record.url?scp=85205256012&partnerID=8YFLogxK
U2 - 10.1002/cmdc.202400218
DO - 10.1002/cmdc.202400218
M3 - Article
SN - 1860-7179
VL - 19
JO - ChemMedChem
JF - ChemMedChem
IS - 22
M1 - e202400218
ER -
