NEW PHTHALOCYANINES FOR PHOTODYNAMIC VIRUS INACTIVATION IN RED BLOOD CELL CONCENTRATES

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Abstract
Cationic phthalocyanines with either aluminum or silicon as the central metal were evaluated for their ability to inactivate viruses in red blood cell concentrates (RBCC) photodynamically. In addition, the virucidal potential of a substituted anionic phthalocyanine, aluminum dibenzodisulfophthalocyanine hydroxide (AlN2SB2POH) was evaluated and compared with that of the much studied anionic aluminum tetrasulfophthalocyanine hydroxide (AIPcS4OH). Based on the rate of inactivation of the lipid-enveloped vesicular stomatitisvirus (VSV), the viruci dal potential of these phthalocyanines was: HOSiPCOSi(CH3)2(CH2)3N+(CH3)3I- (Pc 5) = SiPC[OSi(CH3)2-(CH2)3N+(CH3)3I-]2 (Pc 6) > AIPCOSi(CH,)2(CH2)˜N+(CH3)2(CH˜)11CH3I- (Pc 21) = A1N2SB2POH = AlPcS4 > HOSiPc[OSi(CH3)2(CH2)3N+(CH3)2(CH2)11CH31–]2(Pc 14) > AIPcOSi(CH3)2(CH2)3N+(CHS)3I- (Pc 2). Phthalocy anine ligand 14 and Pc 21 are new phthalocyanines, made by quaternizing known amino analogues. Compared to VSV, the rate of inactivation of Sindbis virus (another model lipid-enveloped virus) was identical when treated in red blood cells (RBC) with Pc 5 and slightly higher when treated with Pc 6 and AlPcS4OH. Treatment of RBCC containing cell-free human immunodeficiency virus (HIV-1) with Pc 5 or AlPcS4OH required 15 min of irradiation to inactivate (>5 log10 reduction) the virus. The extent of HIV-1 inactivation with AlN2SB2POH was 3.7 log10 after 60 min of red light exposure. The RBC integrity after photosensitization was measured by the ability of the cells to bind to plates coated with poly-L-lysine, (which reflects the retention of the RBC surface negative charges) and hemolysis of the cells over a 7 day storage period. The RBC damage using these criteria was most pronounced with Pc 5 and Pc 6 but could be reduced when treatment was in plasma instead of buffer. These data indicate that lipid-enveloped viruses differ in their sensitivity to phthalocyanine photosensitization. Therefore, for virus sterilization of RBCC for transfusion the ability to inactivate human pathogenic viruses completely will have to be evaluated for each virus. The cationic Pc 5 appears to be a potentially useful virucidal agent.