Progress on carboxyl-substituted phthalocyanine photosen-sitizers and their drug delivery systems for photodynamic therapy

Photodynamic therapy (PDT), a photochemical treatment modality centered on photosensitizers, is increasingly demonstrating its significant value in treating malignant tumors and microbial infections. Phthalocyanine compounds, as outstanding representatives of traditional photosensitizers, have attracted considerable attention due to their excellent photophysical and photochemical properties. However, the hydrophobicity of their macrocyclic aromatic planes often leads to intermolecular aggregation, reducing reactive oxygen species (ROS) generation efficiency and impairing drug bioavailability. To address this limitation, carboxylation of the phthalocyanine ring periphery provides amidation sites, facilitating further functionalization and enabling combination with diverse materials, thereby expanding the application potential of phthalocyanine photosensitizers. Additionally, carboxyl substitution enhances the biocompatibility of phthalocyanine photosensitizers and helps mitigate the aggregation problem caused by their hydrophobic nature. Modification strategies for carboxyl-substituted phthalocyanines span multiple fields, including organic chemistry, biomacromolecules, polymeric materials, and inorganic nanomaterials. Based on our team's research, this review delves into the advances in preparation techniques and delivery systems for carboxyl-substituted phthalocyanine photosensitizers and their derivatives. It comprehensively analyzes their advantages and challenges in PDT and imaging systems, aiming to provide technical support and novel perspectives for the development and application of this class of photosensitizers, promote the advancement of PDT in fields such as malignant tumor and microbial infection treatment, drive innovation and application of related technologies, and offer more effective means and strategies for addressing clinical challenges.