Plasma Membrane Properties Involved in the Photodynamic Efficacy of Merocyanine 540 and Tetrasulfonated Aluminum Phthalocyanine

Abstract

Merocyanine 540 (MC540)-mediated photodynamic damage to erythrocytes was strongly reduced when illumination was performed at pH 8.5 as compared to pH 7.4. This could be explained by high pH-mediated hyperpolarization of the erythrocyte membrane, resulting in decreased MC540 binding at pH 8.5. In accordance, the MC540-mediated photooxidation of open ghosts was not inhibited at pH 8.5. Photoinactivation of vesicular stomatitis virus (VSV) was not inhibited at pH 8.5. This suggests that illumination at increased pH could be an approach to protect red blood cells selectively against MC540-mediated virucidal phototreatment. With tetrasulfonated aluminum phthalocyanine (AIPcS4) as photosensitizer, damage to erythrocytes, open ghosts and VSV was decreased when illuminated at pH 8.5. A decreased singlet oxygen yield at high pH could be excluded. The AIPcS4-mediated photooxidation of fixed erythrocytes was strongly dependent on the cation concentration in the buffer, indicating that the surface potential may affect the efficacy of this photosensitizer. This study showed that altering the environment of the target could increase both the efficacy and the specificity of a photodynamic treatment.

Inactivation ofPlasmodium falciparumby Photodynamic Excitation of Heme‐Cycle Intermediates Derived from δ‐Aminolevulinic Acid

“…The photosensitizing dye merocyanine 540, when taken up by cultured P. falciparum and activated by white light, caused a 3-log decrease in viability [43]. However, merocyanine 540 appeared to have little specificity to infected RBCs, as the singlet oxygen produced by this compound was subsequently shown to damage uninfected erythrocytes as well [44][45][46][47]. Further development of pheophorbide derivatives [48] and silicon phthalocyanines [49,50], with respect to the photoinactivation of P. falciparum, have not appeared in the literature.…”

The correlation between photosensitizers' membrane localization, membrane-residing targets, and photosensitization efficiency

“…It was demonstrated with amphiphilic sensitizers, that PDT's lethal action and the injury which is caused leads to damage of transport mechanisms, depolarization of electric potential and leakage across the cytoplasmic and intracellular membranes [23][24][25][26][27][28][29][30][31][32] . It is obvious that depolarization of the cell's electric potential and free passage of ions and molecules through the cytoplasmic membrane are mutually connected.…”