Synthesis and In Vitro Photodynamic Activities of an Integrin‐Targeting cRGD‐Conjugated Zinc(II) Phthalocyanine

A 1,4‐disubstituted zinc(II) phthalocyanine conjugated with a cyclic Arg‐Gly‐Asp‐ D ‐Phe‐Lys (cRGDfK) moiety through a triazole linker was prepared and characterized by UV/Vis spectroscopy and high‐resolution ESI‐MS. The conjugate showed a relatively weak fluorescence emission in N , N ‐dimethylformamide ( Φ F =0.08), but it was a very efficient singlet oxygen generator ( Φ Δ =0.80) as a result of the di‐α‐substituted structure. Owing to the presence of the cyclic peptide sequence cRGDfK, which is a well‐known α v β 3 ‐integrin antagonist, this conjugate exhibited significantly higher cellular uptake toward the α v β 3 + U87‐MG cells compared with the α v β 3 − MCF‐7 cells, as determined by flow cytometry and fluorescence microscopy. The photocytotoxicity of this compound against these two cell lines, however, was comparable owing to the similar efficiency of intracellular reactive oxygen species generation. Confocal microscopic studies also revealed that this conjugate localized preferentially in the lysosomes, but not in the nucleus, endoplasmic reticulum, and mitochondria of the U87‐MG cells.