Silicon Phthalocyanines Axially Disubstituted with Erlotinib toward Small‐Molecular‐Target‐Based Photodynamic Therapy

Abstract Small‐molecular‐target‐based photodynamic therapy—a promising targeted anticancer strategy—was developed by conjugating zinc(II) phthalocyanine with a small‐molecular‐target‐based anticancer drug. To prevent self‐aggregation and avoid problems of phthalocyanine isomerization, two silicon phthalocyanines di‐substituted axially with erlotinib have been synthesized and fully characterized. These conjugates are present in monomeric form in various solvents as well as culture media. Cell‐based experiments showed that these conjugates localize in lysosomes and mitochondria, while maintaining high photodynamic activities (IC50 values as low as 8 nm under a light dose of 1.5 J cm−2). With erlotinib as the targeting moiety, two conjugates were found to exhibit high specificity for EGFR‐overexpressing cancer cells. Various poly(ethylene glycol) (PEG) linker lengths were shown to have an effect on the photophysical/photochemical properties and on in vitro phototoxicity.