Tetra(3,4-pyrido)porphyrazines Caught in the Cationic Cage: Toward Nanomolar Active Photosensitizers
Language English Country United States Media print-electronic
Document type Journal Article
- MeSH
- 3T3 Cells MeSH
- Endothelial Cells drug effects MeSH
- Photochemotherapy MeSH
- Photosensitizing Agents chemical synthesis chemistry pharmacology MeSH
- HeLa Cells MeSH
- Cations chemical synthesis chemistry pharmacology MeSH
- Humans MeSH
- Metalloporphyrins chemical synthesis chemistry pharmacology MeSH
- MCF-7 Cells MeSH
- Molecular Structure MeSH
- Mice MeSH
- Tumor Cells, Cultured MeSH
- Pyridines chemical synthesis chemistry pharmacology MeSH
- Cell Survival drug effects MeSH
- Dose-Response Relationship, Drug MeSH
- Structure-Activity Relationship MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Photosensitizing Agents MeSH
- Cations MeSH
- Metalloporphyrins MeSH
- Pyridines MeSH
Investigation of a series of tetra(3,4-pyrido)porphyrazines (TPyPzs) substituted with hydrophilic substituents revealed important structure-activity relationships for their use in photodynamic therapy (PDT). Among them, a cationic TPyPz derivative with total of 12 cationic charges above, below and in the plane of the core featured a unique spatial arrangement that caught the hydrophobic core in a cage, thereby protecting it fully from aggregation in water. This derivative exhibited exceptionally effective photodynamic activity on a number of tumor cell lines (HeLa, SK-MEL-28, A549, MCF-7) with effective concentrations (EC50) typically below 5 nM, at least an order of magnitude better than the EC50 values obtained for the clinically approved photosensitizers verteporfin, temoporfin, protoporphyrin IX, and trisulfonated hydroxyaluminum phthalocyanine. Its very low dark toxicity (TC50 > 400 μM) and high ability to induce photodamage to endothelial cells (EA.hy926) without preincubation suggest the high potential of this cationic TPyPz derivative in vascular-targeted PDT.
References provided by Crossref.org
Tuning Photodynamic Properties of BODIPY Dyes, Porphyrins' Little Sisters
Peripherally Crowded Cationic Phthalocyanines as Efficient Photosensitizers for Photodynamic Therapy
