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.
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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]34- and Gd43+ [AlPCS4]34- (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]34- (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]34- 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
- Strong 1O2 production upon green or red-light irradiation with quantum yields similar to the conventional molecules in solution
- Content of photocatalytic active porphyrins/phthalocyanine >80%
- Gd43+[AlPCS4]34- 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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Publikationen & Verweise
1) Saline Hybrid Nanoparticles with Phthalocyanine and Tetraphenylporphine Anions Showing Efficient Singlet-Oxygen Production and Photocatalysis; Chem. Commun. 2018, 54, 1245–1248.
2) Gd43+ [AlPCS4]34- Nanoagent Generating 1O2 for Photodynamic Therapy; Adv. Funct. Mater. 2018, doi.org/10.1002/adfm.201801074.
3) Tin Tungstate Nanoparticles: A Photosensitizer for Photodynamic Tumor Therapy.
ACS Nano. 2016 Mar 22; 10(3):3149-57. doi: 10.1021/acsnano.5b03060. Epub 2016 Feb 25
4) In-vitro Fluorescence and Phototoxicity of ß-SnWO4 Nanoparticles
Chem. Commun. 2014, 50, 6600–6603.
- WO 2009/100800 anhängig
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StichworteHybrid Nanoparticles, daylight-activated photocatalysts, selective oxidation, photocatalytic degradation, photodynamic therapy, PDT, biocompatibility, cell membrane permeability