Pivotal Role of the Intracellular Microenvironment in the High Photodynamic Activity of Cationic Phthalocyanines
Dmitry A. Bunin, Roman Akasov, Alexander G. Martynov, Maria Stepanova, Svetlana V. Monich, А. Yu. Tsivadze, Yulia G. Gorbunova
Abstract
To investigate the influence of phthalocyanine aggregation on their photodynamic activity, a series of six cationic water-soluble zinc(II) phthalocyanines bearing from four to sixteen 4-((diethylmethylammonium)methyl)phenoxy substituents was synthesized. Depending on their structure, the phthalocyanines have different aggregation behaviors in phosphate buffer solutions ranging from fully assembled to monomeric states. Remarkably, independent of aggregation in buffer, very high photodynamic efficiencies against the tumor cell lines MCF-7 and MDA-MB-231 in the nanomolar range were found for all investigated phthalocyanine, and the IC 50 (light) varied from 27 to 358 nM (3.5 J/cm 2, 660 nm) with IC 50 (dark)/IC 50 (light) ratios up to ∼3700. This is due to the intracellular disassembly of aggregated phthalocyanines with the formation of monomeric photoactive forms, as demonstrated by fluorescence microscopy. Indeed, the interaction of aggregated phthalocyanines with serum proteins in a buffer resulted in the disassembly of nonluminescent aggregate species with the release of photoactive monomers bound to protein macromolecules.