Recent advancements of porphyrin-based supramolecular nanomaterials for phototherapy

Porphyrins, a class of heterocyclic compounds featuring a large conjugated system, are widely distributed in nature and possess good biocompatibility. Owing to the excellent optical properties, porphyrins and their derivatives exhibit great potential in photodynamic therapy (PDT) and photothermal therapy (PTT). However, although many of the first- and second-generation of porphyrins have been approved for clinical applications, these free porphyrin small molecules have limitations in phototherapy performances, such as poor water solubility and facile aggregation. The supramolecular assembly strategy constructs functional nanostructures via hydrogen bonds, π–π stacking and other non-covalent bond interactions, effectively surmounting these limitations. Herein, firstly, the basic structures and photophysical properties of porphyrins and their derivatives are introduced. Subsequently, the strategies for constructing porphyrin-based supramolecular nanostructures through different approaches are discussed in detail, including: (1) Self-assembly of small molecule porphyrins; (2) Self-assembly of porphyrin-containing macrocyclic compounds; (3) Self-assembly of polymeric porphyrins or porphyrin-encapsulated polymers; (4) Self-assembly of porphyrin-involved host–guest complexes. These strategies not only enhance the phototherapy performances of porphyrins but also integrate phototherapy with chemotherapy, photoimmunotherapy, biofilm eradication, and metabolic modulation to combat drug resistance and hypoxia. Finally, the existing challenges of porphyrin-based supramolecular assemblies in the field of phototherapy are summarized, and future research directions are proposed. By continuously optimizing the assembly strategy and designing novel porphyrin-based supramolecular nanomaterials, it is anticipated to offer more efficient and safe treatment options for the future clinical tanslation. This review focuses on overcoming the limitations of the first- and second-generation of porphyrins via non-covalent strategies and endowing them with new functions, integrating phototherapy with chemotherapy, immunotherapy, biofilm eradication, and metabolic modulation to combat drug resistance and hypoxia. • Supramolecular solutions overcome the limitations of porphyrins in phototherapy. • Integration of phototherapy with other treatments can combat drug resistance and hypoxia. • Continuously optimized assembly strategies will offer more efficient options for clinical translation.