Peripheral and axial substitution of phthalocyanines with solketal groups: synthesis and in vitro evaluation for photodynamic therapy.
Phthalocyanines (Pcs) are a class of photosensitizers (PSs) with a strong tendency to aggregate in aqueous environment, which has a negative influence on their photosensitizing ability in photodynamic therapy. Pcs with either peripheral or axial solketal substituents, that is, ZnPc(sol)8 and Si(sol)2Pc, respectively, were synthesized and their tendency to aggregate as well as their photodynamic properties in 14C and B16F10 cell lines were evaluated. The results were compared to more hydrophilic silicon Pcs, that is, Si(PEG750)2Pc and Pc4. The order of cellular uptake was Pc4 > ZnPc(sol)8 > Si(PEG750)2Pc > Si(sol2)Pc. In contrast, Si(sol2)Pc showed the highest photocytotoxicity, while ZnPc(sol)8 did not show any photocytotoxicity up to a concentration of 10 microM in both cell types. UV/vis spectroscopy showed that Si(sol)2Pc is less prone to aggregation than ZnPc(sol)8, which can explain the lack of photoactivity of the latter. Si(sol)2Pc was predominantly located in lipid droplets, whereas Si(PEG750)2Pc was homogeneously distributed in the cytosol, which is probably the main cause of their difference in photoactivity. The very high photodynamic efficacy of Si(sol)2Pc makes this PS an interesting candidate for future studies.
Hofman
Jan-Willem
JW
Department of Pharmaceutics, Utrecht Institute of Pharmaceutical Sciences (UIPS), Utrecht University, Post Office Box 80082, 3508 TB Utrecht, The Netherlands.
van Zeeland
Femke
F
Turker
Selcan
S
Talsma
Herre
H
Lambrechts
Saskia A G
SA
Sakharov
Dmitri V
DV
Hennink
Wim E
WE
van Nostrum
Cornelus F
CF
D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D017646:Organosilicon Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry; D015032:Zinc
D007211:Indoles; D009942:Organometallic Compounds; D017646:Organosilicon Compounds; D017319:Photosensitizing Agents; C107448:phthalocyanine Pc 4; D011092:Polyethylene Glycols; D015032:Zinc