Hydrophilic vs. amphiphilic anionic Zn(II) phthalocyanines for photodynamic therapy

Two sets of water-soluble zinc (II) phthalocyanines (Zn[II]Pcs) were synthesized and examined for use as photosensitizers in photodynamic therapy. These Zn(II)Pcs contained numerous negatively charged electron-withdrawing carboxylic acid substituents in a rigid arrangement at peripheral positions, subsequently converted into sodium salts. Additionally, the impact of the number and distribution of charged groups on the planar hydrophobic core was examined to assess their influence on the photophysical properties and self-aggregation behavior of the Pcs in an aqueous media. The photophysical findings indicate that the amphiphilic macrocycles ( 2A , 3A , and 4A ) produce more singlet oxygen than the hydrophilic ones ( 2H , 3H , and 4H ) in DMF. The photodynamic activity of sodium salts of Zn(II)Pcs bearing anionic substituents (compounds 4A and 4H ) was evaluated in vitro against oral squamous cell carcinoma (SCC-9) and mouse fibroblast (L-929) cell lines to help elucidate the cell death mechanism. The results confirmed that 4A exhibits high selectivity and efficiency in causing phototoxicity, with an IC 50 value of around 3.8 μM. This work provides new insights into the advanced development of dual-directional ZnPc-based photodynamic therapy agents for treating oral squamous cell cancer. • Synthesized two sets of anionic Zn(II) phthalocyanines with amphiphilic and hydrophilic substituents. • Investigated their photophysical properties, aggregation behavior, and singlet oxygen generation. • Amphiphilic ZnPc (4A) showed high selectivity toward SCC-9 oral cancer cells, with an IC50 of 3.8 μM. • Demonstrated low cytotoxicity in normal fibroblast cells (L-929), confirming biocompatibility.