Add time:08/06/2019         Source:sciencedirect.com

A series of novel symmetric or unsymmetric silicon (IV) phthalocyanines axially substituted with cyclic Arg-Gly-Asp (cRGD) ligands through different ethylene glycol chains have been synthesized by a facile and mild “click” reaction. All the compounds show efficient photosensitizing activities in N,N-dimethylformamide, and are essentially non-aggregated in RPMI 1640 medium with 0.05% Cremophor EL. Owing to the presence of two cRGD ligands, the conjugate 6b exhibits highest selectivity toward αvβ3+ HT-29 cells in photocytotoxicities. It shows higher cellular uptake and ROS generation efficiency toward the αvβ3+ HT-29 cells compared with that of αvβ3- MCF-7 cells. The competitive cellular uptake and subcellular localization indicate that 6b is internalized mainly through integrin-mediated endocytosis. In addition, the in vivo studies showed that 6b can mainly accumulate in tumor sites and show a significant PDT effect resulting in 75% tumor growth inhibition. The results indicate that 6b is a highly promising photosensitizer for targeted photodynamic therapy.

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