Abstract

Gd-4(3+)[AlPCS4](3)(4-) (AlPCS4: aluminium(III) chlorido phthalocyanine tetrasulfonate) inorganic-organic hybrid nanoparticles (IOH-NPs) are presented as a novel photosensitizer for singlet oxygen (O-1(2)) 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 O-1(2) generation. In vitro studies (HepG2 and HeLa cells) demonstrate excellent uptake, low cytotoxicity, and a remarkable induced phototoxicity. Most interestingly, Gd-4(3+)[AlPCS4](3)(4-) 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., Gd-4(3+)[AlPCS4](3)(4-): LD50 5 x 10(-6) m; H4AlPCS4: LD50 > 20 x 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 Gd-4(3+)[AlPCS4](3)(4-) IOH-NPs.