Synthesis and cellular studies of a carboranylchlorin for the PDT and BNCT of tumors.
The syntheses of closo- and nido-carboranylchlorins 4 and 5 from a known carboranylporphyrin are described. Water-soluble nido-carboranylporphyrin 5 was found to have very low dark cytotoxicity (IC50 > 500 microM using a MTT-based assay) but to be toxic in the presence of red light (IC50 = 80 microM at 0.55 J/cm2 light dose). Under the same experimental conditions, carboranylchlorin 5 was taken up by human glioma T98G cells to a significantly higher extent than chlorin e6, a chlorophyll degradation product. The preferred sites of subcellular localization of carboranylchlorin 5 were found to be the cell lysosomes. Our results suggest that carboranylchlorin 5 is a promising new dual sensitizer for the PDT and BNCT treatment of tumors.
Luguya
Raymond
R
Department of Chemistry, Louisiana State University, Baton Rouge, LA 70803, USA.
Jensen
Timothy J
TJ
Smith
Kevin M
KM
Vicente
M Graça H
MG
D045744:Cell Line, Tumor; D006801:Humans; D020128:Inhibitory Concentration 50; D008665:Metalloporphyrins / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009570:Nitriles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D010778:Photochemotherapy; D011838:Radiation-Sensitizing Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013997:Time Factors
D008665:Metalloporphyrins; D009570:Nitriles; D011838:Radiation-Sensitizing Agents; C514203:trans-2,3-dihydro-2,3-bis(dicyanomethyl)-5,10,15,20-tetra((4-nido-carboranyl)phenyl) chlorin; C514202:trans-2,3-dihydro-2,3-bis(dicyanomethyl)-5,10,15,20-tetra((4-o-carbonyl)phenyl)chlorin