Positively charged porphyrins: a new series of photosensitizers for sterilization of RBCs.
BACKGROUND
Photodynamic treatment could be a way to inactivate pathogens in RBCs. The objective of this study was to characterize the virucidal activity and RBC-damaging activity of a series of cationic porphyrins. Using the most efficacious photosensitizer, various in-vitro human RBC quality variables and in-vivo RBC survival in Rhesus monkeys were evaluated.


METHODS
RBCs, spiked with 5 log of extracellular VSV, were treated with porphyrins (25 micro mol/L) and red light (100 W/m2) and essayed for virucidal activity. In-vitro RBC quality variables were assessed during 5 weeks of storage in various ASs. In-vivo survival was investigated with autologous RBCs in Rhesus monkeys.


RESULTS
Tri-P(4) was by far the best sensitizer of a series tested, giving the least hemolysis under conditions that resulted in 5 log-kill of extracellular VSV. Under our experimental conditions, the percentage hemolysis in treated cells was 5.1 +/- 1.1 percent after 5 weeks of storage in SAG-M compared to 1.9 +/- 1.1 percent in the untreated control. Storage in AS-3 resulted hemolysis of 2.3 +/- 1.9 percent. With the exception of IgG binding and potassium leakage, RBC quality variables remained unchanged after photodynamic treatment. Addition of reduced glutathione (GSH) during treatment reduced IgG binding. The 24-hour recovery and T50 of treated RBCs in Rhesus monkeys were satisfactory.


CONCLUSIONS
Porphyrin Tri-P(4) may be a suitable photosensitizer for sterilization of RBCs. However, further exploration to optimize the method is necessary to reach clinically acceptable goals.
Trannoy
Laurence L
LL
Department of Research and Development, Sanquin Blood Supply Foundation, Blood bank South-west, Leiden, the Netherlands. laurence.trannoy@bloodrtd.nl
Lagerberg
Johan W M
JW
Dubbelman
Tom M A R
TM
Schuitmaker
Hans J
HJ
Brand
Anneke
A
D000818:Animals; D004912:Erythrocytes / Q000187:drug effects* / Q000821:virology*; D006384:Hemagglutination; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D008253:Macaca mulatta; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011166:Porphyrins / Q000494:pharmacology*; D011188:Potassium / Q000097:blood; D013242:Sterilization; D014721:Vesicular stomatitis Indiana virus / Q000187:drug effects*
D007074:Immunoglobulin G; D017319:Photosensitizing Agents; D011166:Porphyrins; D011188:Potassium