Photodynamic therapy of viral contaminants with potential for blood banking applications

Abstract

A photodynamic method has been evaluated as a means of eradicating viral contaminants with the potential for rendering blood safe for transfusion. Herpes simplex virus type 1 (HSV-1) was tested under flowing conditions in culture media or in blood supplemented with the virus. Hematoporphyrin derivative was used as the sensitizer and was photoactivated with visible light at 630 nm and 5 J/cm2. HSV-1 in suspension both in culture medium as well as in blood was shown to be killed. The human immunodeficiency virus was also found to be photoinactivated in flowing cell culture medium and, thus, potentially may be inactivated in blood. These findings extend our previous studies which demonstrated that enveloped viruses can be photoinactivated with hematoporphyrin derivative in a static fluid system. Analysis of blood cell number, red cell lysis, plasma proteins, and other standard hematological tests showed no significant change. The possibility that transfusion-associated acquired immunodeficiency syndrome (AIDS) may result from a blood unit infected with human immunodeficiency virus that tested negative makes it imperative that a safe and effective means of viral killing be developed. The system reported here offers promise as an effective approach to this problem.

Importance of Type I and Type Ii Mechanisms in the Photodynamic Inactivation of Viruses in Blood With Aluminum Phthalocyanine Derivatives

“…with photodynamically active dyes. Studies with hematoporphyrin derivative (HPD), Photofrin 11, and merocyanine 540 (MC540) demonstrated the virucidal potential of these compounds when treating culture media and their general compatibility with RBCC; however, virus kill was substantially suppressed in the presence of RBCC and/or plasma (Matthews et al, 1988;Cole et al, 1989;Prodouz 1989;Moroff et al, 1989). We have shown that excellent virus kill can be achieved using aluminum phthalocyanine derivatives whose absorption spectra are red-shifted relative to the absorption maximum of hemoglobin.…”

Photooxidation Products of Merocyanine 540 Formed Under Preactivation Conditions for Tumor Therapy

“…Recently it has been reported that Merocyanine 540 (MC540)t 1 can be photoactivated to give a product which will afterwards in the dark kill tumor cells (70-90%) of different lines, while normal human mononuclear cells survive (85%) (Gulliya et al, 1990a,b). These results are interesting as they might provide an improved procedure for the photodynamic therapy of tumors (PDT) (Dougherty, 1987) and the inactivation of viruses in transfusion blood (Matthews et al, 1988), as well as a better understanding of the photophysiological activity of MC540 1.…”

Can biowarfare agents be defeated with light?

“…214 PDI of viruses has been of special interest for applications in blood banking sterilization. 215 Therefore, several types of virus have been tested for PDI. 215 Ebola The filoviruses, Marburg and Ebola, are classified as Category A biowarfare agents by the Centers for Disease Control.…”

“…215 Therefore, several types of virus have been tested for PDI. 215 Ebola The filoviruses, Marburg and Ebola, are classified as Category A biowarfare agents by the Centers for Disease Control. Most known human infections with these viruses have been fatal (fatality rates for humans of up to 90%) and no vaccines or effective therapies are currently available.…”