Anti-Psoriasis Effects Of α-(8-Quinolinoxy) Zinc Phthalocyanine (ZnPc-F7) Photodynamic Therapy And Its Mechanisms

[Objective] Both a-(8-quinolinoxy) zinc Phthalocyanine (ZnPc-F7) and Sinoporphyrin Sodium (DVDMS-2) are novel photosensitizers invented by Chinese scientists.. Photodynamic Therapy (PDT) used in the treatment of psoriasis is one of the hot research topic at present. The objective of this task is to study the anti-psoriasis effects of ZnPc-F7-PDT in addition to reveal its mechanisms and compare those to DVDMS-2-PDT.[Methods] Using spectrophotometer to measure the photo bleaching characters of ZnPc-F7 and DVDMS-2 in different solutions. Observe the damage effects of 670 nm semiconductor laser to rat skin under different light conditions; determine the affects of output power, irradiation time and light spot diameter. The small animals living imaging measurement system were used to measure the absorption and bleaching of ZnPc-F7 and DVDMS-2 in normal or psoriasis animals in vivo. HaCaT and KB cells were used to observe the influence of ZnPc-F7-PDT and DVDMS-2-PDT on cell proliferation. The anti-psoriasis of ZnPc-F7-PDT and DVDMS-2-PDT were evaluate using mice vaginal epithelium proliferation model, mice tail scale particle formation model, Imiquimod (IMQ) induced nude mice psoriasis model and propranolol induced guinea pigs psoriasis model. Flow cytometry were used to determine the lymphocytes level of mice blood and Western Blot and Polymerase Chain Reaction (PCR) techniques were used to determine the Proliferating Cell Nuclear Antigen (PCNA), B-cell Lymphoma-2 (Bcl 2) family proteins expression and Interleukin (IL) 17 A,17F mRNA expression level change respectively.[Results] The photobleaching speed of ZnPc-F7 significantly faster than DVDMS-2 in normal saline, RPMI-1640 media,1640 medium containing Fetal Bovine serum (FBS) and HaCaT cells suspension, a two-phase bleaching were observe which first fast then slower, the character accorded with secondary dynamics that suggested ZnPc-F7were suitable to use in PDT.670 nm semiconductor laser with different light conditions could cause rat skin Ⅰ°～Ⅳ° burns and the burn depth were directly proportional to irradiation time, output power, the skin surface temperature but inversely proportional to the light spot diameter. The concentrations of ZnPc-F7 and DVDMS-2 in mice skin achieved high values 6 hours after intravenous injection and suitable to operate PDT. ZnPc-F7 and DVDMS-2 distributed to main organs like heart, liver, spleen, lung, kidney, skin and reproductive system after intravenous injection and the fluorescence in psoriasis animal’s skin were uniform. Local skin administration has good bioavailability in skin tissue as well as intravenous delivery. Light exposure after intravenous injection of 6 h, both ZnPc-F7 and DVDMS-2 showed fluorescence bleaching in psoriasis skin tissue. ZnPc-F7-PDT and DVDMS-2-PDT could significantly inhibit HaCaT and KB cell proliferation, when the light doses were fixed, change the irradiation time and output power has little influence on the of inhibition rate. ZnPc-F7-PDT and DVDMS-2-PDT can significantly inhibit mouse vaginal epithelial cells excessive proliferation induced by diethylstilbestrol, psoriasis symptoms induced by IMQ on mice and propranolol induced on guinea pigs, but no significant influence on the formation mouse tail scale granular layer. IMQ induced animals spleen swelling, reduced serum CD4+cells and increased CD8+cells thus the CD4+/CD8+ ratio were decreased, however, in the mice vaginal epithelium experimental, the levels of CD4+, CD8+ and CD4+/CD8+ ratio has no obvious difference in different groups. ZnPc-F7-PDT and DVDMS-2-PDT inhibits the spleen swelling caused by IMQ, increase animal serum level of CD4+,reduce the level of CD8+ and let the CD4+/CD8+ratio return to normal, for vaginal epithelial model animals no obvious effect on serum levels of T lymphocyte were observed. IMQ induced PCNA and Bcl protein expression level and IL-17 A mRNA, IL-17F mRNA expression level up-regulation but the Bax protein expression were down-regulated. ZnPc-F7-PDT and DVDMS-2-PDT could down-regulate the PCNA, Bcl-2 protein expression and IL-17A mRNA, IL-17F mRNA expression and up-regulate the Bax protein expression.[Conclusion] ZnPc-F7 was suitable to use in PDT as well as DVDMS-2. Both the two photosensitizers exhibit good therapeutic effects on excessive proliferative psoriatic models. Immune regulation effects, inhibition of PCNA protein and IL-17 mRNA expression and apoptosis regulation effects may be the main mechanisms.