Novel Nanoparticulate Photosensitizers for Daylight-driven Activation

Innovative Hybrid Nanoparticles Generating Singlet-Oxygen for Efficient Photodynamic Therapy (PDT):
These two novel types of nanomaterials and efficient daylight-activated photocatalysts are activated by blue, green, and even red light.
They exhibit high photostability and excellent uptake into cells, while the systemic toxicity is low. The concept offers new approaches to the treatment of near-surface tumors as well as for inter- or post-surgery killing of individual remaining cancer cells.

Photocatalysts are highly relevant for a wide range of applications, such as selective oxidation (e.g. in organic synthesis), photocatalytic degradation of organic mole­cules and germs (e.g. for water purification), or photo­dynamic therapy (e.g. for tumor therapy). Especially, daylight-activated photocatalysts are highly promising due to the ubiquitious availability of daylight and its less harmful interaction with tissue.

In general, two classes of photosensitizers are widely discussed: molecular photosensitizers (most often por­phyrine-based), and inorganic nanoparticles, including various metal oxides (e.g. TiO₂, ZnO, BiVO₄, Ag₃PO₄). Molecular photosensitizers are also often encapsulated in an inorganic matrix (e.g. SiO₂, Fe₂O₃). These types of photosensitizers exhibit specific disadvantages, such as the presence of harmful and/or expensive metals, low photostability, limited cell uptake, high systemic toxicity, heavy agglomeration under physiological conditions due to strong hydrophobic interaction (e.g. porphyrins) or low colloidal stability (e.g. nanoparticles). Inorganic oxide nanoparticles often suffer from UV-light activation, having a limited penetration depth and being harmful to cells and tissue.
All in a nutshell, there is still a strong need for agents with further optimized photophysical characteristics and depth of light penetration.

At the Karlsruher Institut für Technologie (KIT) novel inor­ganic-organic hybrid nanoparticles (IOH-NPs) such as La₄³⁺ [TPPS₄]₃^4- and Gd₄³⁺ [AlPCS₄]₃^4- (AlPCS₄: alu­minium(III) chlorido phthalocyanine tetrasulfonate; TPPS₄: tetraphenylporphine sulfonate) as well as inorganic nano­particles such as β-SnWO₄ and β-SnMoO₄ were devel­oped.
They can be activated by blue to green and even red light. Both systems were also successfully tested in vitro (e.g. HepG2, HeLa cells) and in vivo (e.g. mice, zebrafish). Gd₄³⁺[AlPCS₄]₃^4- (in suspension) significantly outperforms the clinically approved H₄AlPCS₄ (in solution) in terms of photostability, ¹O₂ generation, phototoxic effect in cells as well as suppression of microcapillary networks and vas­cular cord formation.
Due to the fluorescence of AlPCS₄ and the magnetism of Gd³⁺, Gd₄³⁺[AlPCS₄]₃^4- is suitable for multimodal imaging, including optical imaging/OI and magnetic resonance imaging/MRI.
β-SnWO₄ and β-MoWO₄ are especially characterized by excellent phtostability. In contrast to the IOH-NPs, β-SnWO₄ and β-MoWO₄ are activated by blue light, which means a smaller penetration depth into the tissue.

for β-SnWO₄ and β-MoWO₄ 

• Activated by blue light
• High chemical stability
• Excellent photostability

for IOH-NPs

• Strong ¹O₂ production upon green or red-light irradiation with quantum yields similar to the conventional molecules in solution
• Contento_f photocatalytic active porphyrins/phthalocyanine >80%
• Gd₄³⁺[AlPCS₄]₃^4- with LD₅₀ < 5x10^-6 M
• Excellent cell membrane permeability
• High biocompatibility
• Low systemic toxicity
• Lower threshold for approval
• No inhibition of endothelial cell alignment and cord formation in darkness
• Multimodal imaging possible
• Simple, straightforward aqueous synthesis of the IOH-NPs

Here, we present two concepts and novel types of nano­materials as efficient daylight-activated photocatalysts that are activated by blue, green, and even red light. The photocatalysts exhibit high photostability and excellent uptake into cells. Whereas they show high phototoxicity the systemic toxicity is low. Aiming at medicine, specific interest can be related not only to the treatment of near-surface tumors but also to inter- or post-surgery killing of individual cancer cells remaining after extraction of the solid primary tumor.

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