Quinolin-8-yloxy-substituted zinc(II) phthalocyanines for enhanced in vitro photodynamic therapy

Photodynamic therapy (PDT) is an innovative and promising modality to treat various tumors. In this study, two novel zinc(II) phthalocyanines substituted with quinolin-8-yloxy groups at the a-position, namely mono(quinolin-8-yloxy) zinc(II) phthalocyanine (ZnPc-Q1) and tetra(quinolin8- yloxy) zinc(II) phthalocyanine (ZnPc-Q4), have been synthesized and fully characterized. With quinolin-8-yloxy, these two phthalocyanines exhibit less self-aggregation in DMF and culture medium, high singlet oxygen quantum yields, mitochondria localization and high photodynamic activities (IC50 values as low as 2 nM). Compared to ZnPc-Q4, ZnPc-Q1 exhibits higher cellular uptake and lower IC50 values. Benefitting from its higher anticancer efficacy and lack of isomers, ZnPc-Q1 is a highly promising anticancer agent in clinical application.