Tracking Microenvironmental Response on Self-Assembled Phthalocyanine Systems - Adaptive and Non-Adaptive Antibacterial Photosensitization.

Self-assembly has proven to be one of the effective methods for the formation of nanoscale therapeutics without the need to use nanodelivery systems. Such minimal models of supramolecular systems formed from amphiphilic photosensitizers (PS) have recently emerged as a new class of photoactive systems, providing unique and in some cases superior activities. Although the mechanism of photogenerated reactive oxygen species (ROS) in such systems is studied and to a certain extent understood, there are very limited studies investigating the influence of intricate environmental factors, including those occurring in the cellular environment, on the self-assembly and thus the activity of the system. Understanding the optimal conditions for the formation of active PS aggregates is an important area of research in the field of photodynamic therapy (PDT), as it is directly linked to the optimal treatment dose. In this study, we describe the synthesis, self-assembly properties, photophysical characterization, and photobiological efficacy of structurally closely related low-symmetry phthalocyanine derivatives. Studying the decay behavior of the PS fluorescence lifetime in the presence of molecular crowders and different bacterial strains, we found that certain derivatives exhibited adaptive behavior and change in activity, while others demonstrated non-adaptive characteristics.