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.