Advances of light-activated cationic porphyrins and phthalocyanines for cancer photodynamic therapy

Abstract

Cationic porphyrins (Por) and phthalocyanine (Pc) derivatives are photoactive compounds with strong absorption in the UV–Vis region, making them promising candidates for photodynamic therapy (PDT) against cancer cells. Due to less solubility properties of some compounds in aqueous environments, structural modifications are often required to enhance their amphiphilicity and bioavailability. Introducing positively charged groups, such as e.g., pyridinium or ammonium moieties, into the macrocyclic framework significantly improves water solubility and cellular uptake, optimizing their potential for the PDT approach. This review focuses on the recent advancements in the design and application of cationic Por and Pc dyes for PDT of cancer diseases. Several parameters of the different PDT studies with versatile molecules are analyzed and compared across different structural modifications, light absorption properties (Soret and Q bands), singlet oxygen quantum yield (Ф_∆), fluorescence quantum yield (Ф_F), (photo)stability, and attending to the half-maximal inhibitory concentration (IC₅₀). Additionally, the impact of metal insertion and the nature, number, and position of cationic substituents, peripheral or axial, are discussed in relation to their photodynamic performance. Emphasis is placed on structure activity relationships, the selective accumulation in tumor cells, subcellular localization, and phototoxicity under different light irradiation conditions. This review is distinguished by a critical and comparative assessment of the literature, addressing relevant gaps in previous studies, particularly the insufficient and non-systematic determination of key photophysical parameters. Notwithstanding this standpoint, this review underscores the central role of rational molecular design and structure–activity relationships, contributing significantly to the development of efficient and selective cationic photosensitizers and to the advancement of PDT as a minimally invasive and targeted therapeutic strategy.