Resumen de Ruthenium Phthalocyanines as Third-Generation Photosensitizers for Cancer and Antimicrobial Photodynamic Therapy (PDT)
Photodynamic Therapy (PDT) combines light, a photosensitizer (PS) and molecular oxygen to produce reactive oxygen species (ROS) such as singlet oxygen that induce confined cellular damage and dead. This thesis explores the design, synthesis and evaluation of ruthenium phthalocyanine-based photosensitizers (RuPc-PSs) for applications in photodynamic therapy (PDT), antimicrobial photodynamic inactivation (PDI) and theranostics. RuPcs constitute a type of complexes that exhibit high triplet state quantum yields and hence, are efficient singlet oxygen generators. The RuPcs have been donated with axial pyridyl ligands bearing functional groups that have been strategically designed to modulate key physicochemical, photophysical, photochemical and biological properties relevant to PDT, including solubility, aggregation, lipophilicity, orthogonal reactivity, targeted cellular transport and luminescence. The selected functionalities have been attached to the pyridine ring via electron-withdrawing spacers, such as esters or amides, giving electron-deficient pyridine derivatives that enable the preparation of photosensitizers exhibiting high singlet oxygen quantum yields. The research involves the synthesis of glycomultivalent RuPc-based systems and their evaluation for the photodynamic therapy of bladder cancer, the preparation of novel bactericidal agents based on RuPc for antimicrobial PDI, the construction of orthogonal platforms based on RuPcs for their bioconjugation to relevant biomolecules, paving the way to develop methodologies for designing third-generation PSs for PDT, and the creation of potential theranostic agents based on RuPc for in vitro and in vivo applications.
