Fully protected glycosylated zinc (II) phthalocyanine shows high uptake and photodynamic cytotoxicity in MCF-7 cancer cells.
Phthalocyanine photosensitizers are effective in anticancer photodynamic therapy (PDT) but suffer from limited solubility, limited cellular uptake and limited selectivity for cancer cells. To improve these characteristics, we synthesized isopropylidene-protected and partially deprotected tetra β-glycosylated zinc (II) phthalocyanines and compared their uptake and accumulation kinetics, subcellular localization, in vitro photocytotoxicity and reactive oxygen species generation with those of disulfonated aluminum phthalocyanine. In MCF-7 cancer cells, one of the compounds, zinc phthalocyanine {4}, demonstrated 10-fold higher uptake, 5-fold greater PDT-induced cellular reactive oxygen species concentration and 2-fold greater phototoxicity than equimolar (9 μm) disulfonated aluminum phthalocyanine. Thus, isopropylidene-protected β-glycosylation of phthalocyanines provides a simple method of improving the efficacy of PDT.
Department of Life, Health and Chemical Sciences, The Open University, Milton Keynes, UK.
Stanley G
SG
Kimani
Tatiana A
TA
Shmigol
Samantha
S
Hammond
James B
JB
Phillips
James I
JI
Bruce
Alexander J
AJ
MacRobert
Mikhail V
MV
Malakhov
Jon P
JP
Golding
D000475:Alkenes / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001692:Biological Transport; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D006031:Glycosylation; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000494:pharmacology*; D054833:Isoindoles; D007700:Kinetics; D008027:Light; D061986:MCF-7 Cells; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000494:pharmacology*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D017967:Zinc Compounds
D000475:Alkenes; D000970:Antineoplastic Agents; D007211:Indoles; D054833:Isoindoles; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; D017382:Reactive Oxygen Species; D017967:Zinc Compounds; C052159:Zn(II)-phthalocyanine; C060570:aluminum phthalocyanine; C013658:propylene