Erlotinib Analogue-substituted Zinc(II) Phthalocyanines for Small Molecular Target-based Photodynamic Cancer Therapy

"Smart" targeted photosensitizer conjugated with small molecule target-based anticancer drug which has a simple chemical structure and high stability, is a new promising targeted therapeutic strategy. We herein extended this strategy and reported a novel series of zinc(II) phthalocyanine-erlotinib analogue conjugates with different peripheral substituted positions and lengths of the linker. Having erlotinib analogue as the targeting moiety, all conjugates exhibited high specificity and potent affinity to HepG2 cancer cells and kept high photodynamic activity (IC50=3.7 -16.7 nmol/L). Structure-activity relationships of these conjugates were assessed by investigating their photophysical/photochemical properties, targeting intracellular uptake and in vitro phototoxicity. The results suggested that a-substituted conjugates showed slightly higher photodynamic activity than beta-substituted ones. In conclusion, we have developed a series of promising anticancer agents with high tumor selectivity and anticancer activity for targeted photodynamic therapy.