Gd43+[AlPCS4]34− Nanoagent Generating 1O2 for Photodynamic Therapy

Abstract

AbstractGd43+[AlPCS4]34− (AlPCS4: aluminium(III) chlorido phthalocyanine tetrasulfonate) inorganic–organic hybrid nanoparticles (IOH‐NPs) are presented as a novel photosensitizer for singlet oxygen (1O2) generation with potential use in localized photodynamic therapy. The saline nanoparticles contain an unprecedented high phthalocyanine content of 81 wt% AlPCS4; they show red emission (680 nm), and efficient 1O2 generation. In vitro studies (HepG2 and HeLa cells) demonstrate excellent uptake, low cytotoxicity, and a remarkable induced phototoxicity. Most interestingly, Gd43+[AlPCS4]34− IOH‐NPs (in suspension) significantly outperform the clinically approved H4AlPCS4 (in solution) in terms of photostability, reactive oxygen species generation, phototoxic effect in cells (i.e., Gd43+[AlPCS4]34−: LD50 < 5 × 10−6 m; H4AlPCS4: LD50 > 20 × 10−6 m, both illuminated 10 min at 670 nm), as well as suppression of microcapillary networks and vascular cord formation. According to in vivo studies, IOH‐NP‐pretreated HeLa‐GFP cells injected into zebrafish larvae can be easily colocalized based on the red emission of the IOH‐NPs and the green emission of the tumor cells. Upon light exposure (0–20 min at 635 nm), the transgenic HeLa‐GFP cells show drastically reduced viability in vivo due to the induced phototoxicity of the Gd43+[AlPCS4]34− IOH‐NPs.