Molecular-Target-Based Anticancer Photosensitizer: Synthesis and in vitro Photodynamic Activity of Erlotinib-Zinc(II) Phthalocyanine Conjugates

Targeted photodynamic therapy is a new promising therapeutic strategy to overcome growing problems in contemporary medicine, such as drug toxicity and drug resistance. A series of erlotinib-zinc(II) phthalocyanine conjugates were designed and synthesized. Compared with unsubstituted zinc(II) phthalocyanine, these conjugates can successfully target EGFR-overexpressing cancer cells owing to the presence of the small molecular- target-based anticancer agent erlotinib. All conjugates were found to be essentially non-cytotoxic in the absence of light (up to 50 mu m), but upon illumination, they show significantly high photo-cytotoxicity toward HepG2 cells, with IC50 values as low as 9.61-91.77 nm under a rather low light dose (lambda = 670 nm, 1.5 J cm(-2)). Structure-activity relationships for these conjugates were assessed by determining their photophysical/photochemical properties, cellular uptake, and in vitro photodynamic activities. The results show that these conjugates are highly promising antitumor agents for molecular-target-based photodynamic therapy.