Tamoxifen-Zinc(II) phthalocyanine conjugates for target-based photodynamic therapy and hormone therapy

Although photodynamic therapy has been extensively studied in recent years and preclinical studies have shown promising results, strategies for enhancing PDT outcomes and reducing side effects still urgently need to be developed. In this study, a series of Tamoxifen-zinc(II) phthalocyanine conjugates have been designed and synthesized. In these "double-headed" conjugates, photodynamic therapy agent zinc(II) phthalocyanine and hormone therapy drug Tamoxifen were combined via oligoethylene glycol linkers. The conjugates show high specificity, and some of them show cytotoxic effects against the MCF-7 cells overexpressed Estrogen receptor, due to the targeting and cytostatic Tamoxifen moiety. Upon illumination, all these conjugates show high cytotoxicity due to the photosensitizing phthalocyanine unit. Their structure-activity relationship was also assessed. The results show that alpha-substituted Tamoxifenzinc(II) phthalocyanine conjugates are highly promising anticancer targeting agents which exhibit additive effects of photodynamic therapy and hormone therapy.