Small molecular target-based multifunctional upconversion nanocomposites for targeted and in-depth photodynamic and chemo-anticancer therapy.

A novel multifunctional nano-system, ZnPc-UCNPs-PEG-G, was designed for targeted and in-depth photodynamic therapy. The nano-system was built via covalent conjugation, in which phthalocyanine zinc (ZnPc), Gefitinib (G), NaYF4: Yb, Er (UCNPs) and PEG derivatives were employed as the photosensitizer, target moiety, upconversion nanomaterial and linker unit, respectively. The photophysical/chemical properties, in-depth photodynamic activity, cancer cell specificity and anticancer activity of ZnPc-UCNPs-PEG-G were investigated. The as-prepared ZnPc-UCNPs-PEG-G exhibits excellent photosensitizing ability, generating reactive oxygen species (ROS) via effective energy transfer from UCNP to phthalocyanine zinc. In addition, the composite exhibits specific affinity to HepG2 cancer cells and high anticancer activity. To the best of our knowledge, this is the only example of a UCNP platform that is capable of molecular targeted and in-depth photodynamic and chemo-anticancer therapy via the introduction of a small molecular targeting drug moiety.

A Molecular Combination of Zinc(II) Phthalocyanine and Tamoxifen Derivative for Dual Targeting Photodynamic Therapy and Hormone Therapy.

The combination of photodynamic therapy and other cancer treatment modalities is a promising strategy to enhance therapeutic efficacy and reduce side effects. In this study, a tamoxifen-zinc(II) phthalocyanine conjugate linked by a triethylene glycol chain has been synthesized and characterized. Having tamoxifen as the targeting moiety, the conjugate shows high specific affinity to MCF-7 breast cancer cells overexpressed estrogen receptors (ERs) and tumor tissues, therefore leading to a cytotoxic effect in the dark due to the cytostatic tamoxifen moiety, and a high photocytotoxicity due to the photosensitizing phthalocyanine unit against the MCF-7 cancer cells. The high photodynamic activity of the conjugate can be attributed to its high cellular uptake and efficiency in generating intracellular reactive oxygen species. Upon addition of exogenous 17ß-estradiol as an ER inhibitor, the cellular uptake and photocytotoxicity of the conjugate are reduced significantly. As shown by confocal microscopy, the conjugate is preferentially localized in the lysosomes of the MCF-7 cells.