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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 (A1N2SB2POH) was evaluated and compared with that of the much studied anionic aluminum tetrasulfophthalocyanine hydroxide (A1PcS4OH). Based on the rate of inactivation of the lipid-enveloped vesicular stomatitis virus (VSV), the virucidal 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) > A1PcOSi(CH3)2(CH2)3N+(CH3)2(CH2)11CH3I- (Pc 21) = A1N2SB2POH = A1PcS4 > HOSiPc[OSi(CH3)2(CH2)3N+(CH3)2(CH2)11CH3I-]2 (Pc 14) > A1PcOSi(CH3)2(CH2)3N+(CH3)3I- (Pc 2). Phthalocyanine 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 A1PcS4OH. Treatment of RBCC containing cell-free human immunodeficiency virus (HIV-1) with Pc 5 or A1PcS4OH required 15 min of irradiation to inactivate (> 5 log10 reduction) the virus. The extent of HIV-1 inactivation with A1N2SB2POH 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.(ABSTRACT TRUNCATED AT 250 WORDS)

INTRODUCTIONImprovements in donor selection and serological testing for some human pathogens' have resulted in a safer blood supply during the last 10 years. Most importantly, implementation of virucidal procedures for coagulation factor concentrates and plasma have made these blood products completely safe with respect to transmission of hepatitis B virus (HBV),? hepatitis C virus (HCV) and human immunodeficiency virus (HIV).Z.3 However, there are still risks of infection associated with transfusion of cellular blood components, i.e. red blood cell (RBC) concentrates and platelet concentrates. This is due to the inability of serological tests to detect viral infection during the "window" p e r i~d .~ In addition, viruses we do not test for may be present and technical errors may occur, albeit infrequently. In the case of protein blood derivatives and plasma, sterilized by the solvent-detergent technique or heat, there is continued transmission of parvovirus B195 and hepatitis A,6 both of which are nonenveloped and heat-stable viruses, requiring new virucidal procedures.Over the past 5 years, a number of different approaches were explored to inactivate or remove viruses from blood and blood components, including the use of filtration, washing, hydrolyzable diol epoxides, ozone, halogenated oxidizing agents and photochemical treatment^.',^ The most promising results to date have come using photochemical approaches, including UVC and photoactive dyes9 Recent advances in this field over the last 3 years, as well as future prospects, are described below. PLASMA AND BLOOD PROTEINSAs mentioned above, in spite of enhanced safety with regard to transmission of human pathogenic viruses when plasma and blood proteins are treated with the solvent-detergent technique, some concerns remain. In addition to the nonenveloped viruses there is the necessity to pool plasma from *To whom correspondence should be addressed.-FAbbreviations: AHF, antihemophilic factor; AMT, 4'-aminomethyl-4,5',8-trimethylpsoralen; BPD-MA, benzoporphyrin monoacid A; FFP, fresh-frozen plasma; HBV hepatitis B virus; HCV, hepatitis C virus; HIV, human immunodeficiency virus; MB, methylene blue; MC 540, merocyanine 540; 8-MOP, 8-methoxypsoralen; Pc, phthalocyanine; Pc 4, silicon phthalocyanine derivative; PDT, photodynamic therapy; PUVA, psoralen and UVA; RBCC, red blood cell concentrate; VSV, vesicular stomatitis virus. different donors, thus increasing the risk of spreading infectious particles. Two photochemical approaches have been used to address these concerns. UVC irradiationUltraviolet C targets the viral nucleic acid and can inactivate a wide variety of viruses, irrespective of the nature of their envelope, with viruses containing single-stranded nucleic acids being most sensitive.IO As a result, UVC irradiation was the first sterilization method introduced for blood products in 1949." However, by 1955 this was abandoned following the demonstration that adequate sterilization of plasma could only be achieved by UVC doses that inactivated plasma co...

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