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7 August 1992 Biological activity of photoproducts of merocyanine 540 generated by laser-light activation
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Proceedings Volume 1646, Laser-Tissue Interaction III; (1992)
Event: OE/LASE '92, 1992, Los Angeles, CA, United States
Controlled exposure of photoactive compounds to light prior to their use in biological targets results in the formation of heretofore unknown photoproducts. This process of photoproduct generation, termed "preactivation," renders the photactive compound capable of systemic use without further dependence on light. Preactivation of mercyanin 540 (MC540) and several other photoactive compounds is achievable by exposure to CW and pulse laser radiation. The singlet oxygen generated at excited states attacks the dye molucule itself, resulting in the formation of biologically active photoproducts. For preactivated MC540 (photoproducts of MC540) generated by exposure to argon laser light (514 nm) and light from free-electron laser, we have demonstrated its effectiveness in selective killing of certain types of cultured tumor cells as well as human immunodeficiency virus type 1 (HIV-1) with very low, if any, damage to normal cells and tisues. For example, approximately 90% of the Burkitt's lymphoma Daudi cells and HL-60 leukemic cells are killed by preactivated MC540 at a concentration of 120 μg/ml. A two-hour treatment of cultured cells with buthionine sulfoxamine followed by the treatement with preactivated MC540 reults in 99.99% inhibition of clonogenic tumor stem cell growth. We also have demonstrated that preactivated MC540 is very effective in killing cell-free and cell-associated HIV-1. It also is very effective in killing HIV-1 and simian immunodeficiency virus (SIV) in virus-infected blood in vitro as determined by reverse transcriptase, P24, P17, core antigen expression and synctium formation. Treatment of HIV-1 with preactivated MC540 renders the treated HIV-1 incapable of binding to CD4 target molecules on T cells as determined by immunofluorescence and radioimmunoprecipitation assays. In vivo toxicology studies show that preactivated MC540 is very well tolerated and does not produce any signs of adverse reaction at the therapeutic doses, as determined by physical examination, serum eletrolyte measurements, blood chemistry, and histopathology. Photoproducts generated via the process of preactivation are currently under investigation for optimum activity and yield using high-peak, power-pulse lasers.
© (1992) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only.
Kirpal S. Gulliya, Tran C. Chanh, Shazib Pervaiz, Anthony Harriman, and James Lester Matthews "Biological activity of photoproducts of merocyanine 540 generated by laser-light activation", Proc. SPIE 1646, Laser-Tissue Interaction III, (7 August 1992);

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