A Biotinylated and Endoplasmic Reticulum‐Targeted Glutathione‐Responsive Zinc(II) Phthalocyanine for Targeted Photodynamic Therapy

Abstract

A biotinylated glutathione (GSH)-responsive zinc(II) phthalocyanine has been prepared and characterized. With a 2,4-dinitrobenzenesulfonyl moiety, its fluorescence emission and singlet oxygen generation were silenced in its intact state. Upon exposure to high concentration of GSH, its photosensitizing properties were restored in phosphate buffered saline and inside tumor cells. It also showed preferential uptake on HepG2 human hepatocarcinoma cells (with higher biotin receptor expression) rather than Chinese hamster ovary (CHO) cells (with lower biotin receptor expression). Upon irradiation, it caused photocytotoxicity with an IC value down to 0.1 μm on HepG2 cells. Moreover, it can localize in the endoplasmic reticulum (ER), causing ER stress after light irradiation.

Zinc(II) phthalocyanines as photosensitizers for antitumor photodynamic therapy

“…The observation of DOX fluorescence in the nucleus and ZnPc in the cytoplasm demonstrated that acidic and reducing intracellular environments could trigger the release of drugs by cleaving the linkers (Gao and Lo, 2018). A synergistic cytotoxicity was therefore found for certain DOX:ZnPc ratios in tumor-bearing mice.…”

“…: as a key organelle involved both in the folding and trafficking of newly synthesized proteins as well as in the maintenance of Ca 2+ homeostasis, ER photodamage after PDT can contribute to an apoptotic cell death(Buytaert et al, 2007; Moserova and ). In the field of ZnPcs,Yu L et al (2018) reported the ER localization of a biotinylated glutathione-responsive ZnPc that triggers ER stress after light irradiation.…”

Type I photosensitizers based on phosphindole oxide for photodynamic therapy: apoptosis and autophagy induced by endoplasmic reticulum stress

“…[44][45][46] So far, however, except for the representative hypericin, 47 few ER-targeting PSs have been reported because of the unclear targeting mechanism, which remains a challenge. 24,[48][49][50] Therefore, the development of ER-targeting PSs and the investigation of ERmediated PDT are of great signicance.…”

Self-Assembled Nanophotosensitizing Systems with Zinc(II) Phthalocyanine-Peptide Conjugates as Building Blocks for Targeted Chemo-Photodynamic Therapy

“…ZnPcbased photosensitizers were chosen because of their advantageous characteristics, including strong absorption in the red visible region, high ROS generation efficiency, and ease of chemical modification. 24,25 Moreover, the macrocyclic core of phthalocyanines can facilitate the self-assembly via π−π stacking and hydrophobic interactions. The short peptide was utilized to link up the ZnPc and the biotin targeting group, assist the self-assembly process via noncovalent interactions, and provide favorable pharmacological features.…”

“…As an extension of this study, we report herein a series of self-assembled nanophotosensitizing systems consisting of ZnPc molecules conjugated with a short peptide (Gly-Gly-Lys) with either a carboxyl or a carbamoyl group at the C-terminus and appended with a biotin moiety, together with DOX. ZnPc-based photosensitizers were chosen because of their advantageous characteristics, including strong absorption in the red visible region, high ROS generation efficiency, and ease of chemical modification. , Moreover, the macrocyclic core of phthalocyanines can facilitate the self-assembly via π–π stacking and hydrophobic interactions. The short peptide was utilized to link up the ZnPc and the biotin targeting group, assist the self-assembly process via noncovalent interactions, and provide favorable pharmacological features.…”