Effect of overall charge and charge distribution on cellular uptake, distribution and phototoxicity of cationic porphyrins in HEp2 cells.
Five cationic porphyrins bearing one to four -N(CH(3))(3)(+) groups linked to the p-phenyl positions of 5,10,15,20-tetraphenylporphyrin (TPP) were synthesized in order to study the effect of overall charge and its distribution on the cellular uptake, phototoxicity and intracellular localization using human carcinoma HEp2 cells. The di-cationic porphyrins DADP-o and DADP-a accumulated the most within cells and preferentially localize within vesicular compartments and in mitochondria. Of these two only DADP-a was phototoxic to the cells (IC(50)=3 microM at 1 J/cm(2)). The mono-cationic porphyrin MAP was found to be the most phototoxic of the series, and it localized mainly in lipid membranes, including the plasma membrane, ER, mitochondria, and Golgi. Both the tri-cationic porphyrin TRAP and the tetra-cationic porphyrin TEAP localized subcellularly mainly in the mitochondria, but of the two only TEAP showed moderate phototoxicity (IC(50)=8 microM at 1 J/cm(2)). Our results suggest that MAP is the most promising PDT photosensitizer, and that both DADP-o and TRAP might find application as transport vehicles for therapeutics into cells.
Jensen
Timothy J
TJ
Department of Chemistry, Louisiana State University, Baton Rouge, LA 70803, USA.
Vicente
M Graça H
MG
Luguya
Raymond
R
Norton
Jolanna
J
Fronczek
Frank R
FR
Smith
Kevin M
KM
D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D006801:Humans; D008856:Microscopy, Fluorescence; D008968:Molecular Conformation; D017319:Photosensitizing Agents / Q000032:analysis / Q000138:chemical synthesis / Q000633:toxicity*; D011166:Porphyrins / Q000032:analysis / Q000138:chemical synthesis / Q000633:toxicity*; D000644:Quaternary Ammonium Compounds / Q000737:chemistry; D013997:Time Factors
C509964:5,10,15,20-tetraphenylporphyrin; D017319:Photosensitizing Agents; D011166:Porphyrins; D000644:Quaternary Ammonium Compounds; C009571:phenyltrimethylammonium