Identifying Structural Factors Governing the Photodynamic Activity of Phthalocyanines

Phthalocyanines (Pcs) are promising photosensitizers (PSs) for photodynamic therapy (PDT). However, the variability in experimental conditions in in vitro experiments among reported derivatives complicates clear comparisons. In this study, we systematically evaluated a diverse set of more than 40 cationic, anionic, nonionic Zn, Mg, or metal-free or axially substituted silicon Pcs and compared them under standardized conditions. Their spectral and photophysical properties, interactions with bovine serum albumin, subcellular localization, and in vitro PDT efficacy in three human cancer cell lines were assessed. Structural features influencing PDT efficacy include their presence in the monomeric state through axial substitution (in silicon Pcs) or rigid bulky peripheral groups with the latter enhancing activity in cationic derivatives while reducing it in nonionic derivatives. Amphiphilic structures significantly improved the PDT efficacy, especially for nonionic and anionic Pcs. The results of this study provide clear design principles for the future development of highly efficient PSs for PDT.