TY - JOUR
T1 - Exploring Si-phthalocyanines with different valency for PSMA-targeted photodynamic therapy
T2 - Synthesis and preclinical validation
AU - Dinatale, Valentina
AU - Capozza, Martina
AU - Stefania, Rachele
AU - Liuzzi, Simona
AU - de Bruijn, Henriette S.
AU - McMorrow, Roisin
AU - Zambito, Giorgia
AU - Robinson, Dominic
AU - Mezzanotte, Laura
AU - Terreno, Enzo
N1 - Publisher Copyright:
© 2025
PY - 2025/6
Y1 - 2025/6
N2 - Prostate cancer remains a significant health concern, with existing treatments often proving invasive or inadequate in preventing recurrence. This study explores the development and preclinical validation of silicon-phthalocyanine (SiPc)-based photosensitizers (PSs) targeted at prostate-specific membrane antigen (PSMA) for photodynamic therapy (PDT). Two PSMA-targeted SiPcs, monovalent and bivalent, were synthesized with axial conjugation through Si–O–C linkages to evaluate their efficacy and specificity. The bivalent SiPc-PQ-(PSMAi)2 demonstrated superior optical properties, reduced aggregation, and enhanced target specificity compared to the monovalent SiPc-PQ-PSMAi. Cellular and in vivo assays confirmed its high PSMA-specific uptake, potent photoinduced cytotoxicity mediated by reactive oxygen species, and significant tumor growth inhibition post-PDT. These findings underscore the potential of bivalent SiPc-PQ-(PSMAi)2 as an effective agent for targeted PDT, combining imaging and therapeutic capabilities for improved prostate cancer management. Further optimization and clinical evaluation could establish its role in theranostic strategies to enhance surgical outcomes and reduce recurrence.
AB - Prostate cancer remains a significant health concern, with existing treatments often proving invasive or inadequate in preventing recurrence. This study explores the development and preclinical validation of silicon-phthalocyanine (SiPc)-based photosensitizers (PSs) targeted at prostate-specific membrane antigen (PSMA) for photodynamic therapy (PDT). Two PSMA-targeted SiPcs, monovalent and bivalent, were synthesized with axial conjugation through Si–O–C linkages to evaluate their efficacy and specificity. The bivalent SiPc-PQ-(PSMAi)2 demonstrated superior optical properties, reduced aggregation, and enhanced target specificity compared to the monovalent SiPc-PQ-PSMAi. Cellular and in vivo assays confirmed its high PSMA-specific uptake, potent photoinduced cytotoxicity mediated by reactive oxygen species, and significant tumor growth inhibition post-PDT. These findings underscore the potential of bivalent SiPc-PQ-(PSMAi)2 as an effective agent for targeted PDT, combining imaging and therapeutic capabilities for improved prostate cancer management. Further optimization and clinical evaluation could establish its role in theranostic strategies to enhance surgical outcomes and reduce recurrence.
UR - http://www.scopus.com/inward/record.url?scp=105001010941&partnerID=8YFLogxK
U2 - 10.1016/j.ejmech.2025.117562
DO - 10.1016/j.ejmech.2025.117562
M3 - Article
C2 - 40147340
AN - SCOPUS:105001010941
SN - 0223-5234
VL - 290
JO - European Journal of Medicinal Chemistry
JF - European Journal of Medicinal Chemistry
M1 - 117562
ER -
