Synthesis and cellular studies of nonaggregated water-soluble phthalocyanines.
Water-soluble phthalocyanines are promising photosensitizers for application in cancer therapy and in the photoinactivation of viruses. The water-soluble zinc(II) phthalocyanines 5 and 6 were synthesized by converting the corresponding ester derivative 4 into the sodium carboxylate and carboxylic acid species. Compound 5 can be solubilized in water as a monomeric species, as demonstrated by UV/vis and fluorescence spectroscopy. These compounds were characterized by analytical and spectroscopic methods and, in the case of 4, by X-ray crystallography. The water-soluble phthalocyanines were found to have low dark cytotoxicity toward V79 hamster fibroblasts and human HEp2 cells, to be phototoxic at low light and drug doses, to be taken up by cells in culture, and to localize intracellularly, mainly in the cell lysosomes. Conjugation of the anionic phthalocyanines with positively charged LipoGen liposomes resulted in effective delivery of these compounds into the nuclei of cells. It is concluded that these highly water-soluble phthalocyanines are promising sensitizers for the photodynamic therapy of tumors.
Liu
Wei
W
Louisiana State University, Department of Chemistry, Baton Rouge, Louisiana 70803, USA.
Jensen
Timothy J
TJ
Fronczek
Frank R
FR
Hammer
Robert P
RP
Smith
Kevin M
KM
Vicente
M Graça H
MG
D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D018360:Crystallography, X-Ray; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008027:Light; D008247:Lysosomes / Q000378:metabolism; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017319:Photosensitizing Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D012995:Solubility; D013053:Spectrophotometry; D013329:Structure-Activity Relationship
D007211:Indoles; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; C498567:zinc(II) 2,3,9,10,16,17,23,24-octa((3,5-biscarboxyate)phenoxy)phthalocyanine