Next-generation photodynamic cancer therapy: purpurin-based nanocarriers as emerging photosensitizers

Cancer remains a leading global health burden, with approximately 20 million new cases and 9.7 million deaths reported in 2022, and projections indicating a substantial rise by 2050. Nearly one in five individuals is expected to develop cancer during their lifetime, underscoring the urgent need for more effective and targeted therapies. Photodynamic therapy (PDT) has emerged as a minimally invasive modality that utilizes photosensitizers, light, and oxygen to generate cytotoxic reactive oxygen species (ROS) for localized tumor destruction. However, conventional photosensitizers are limited by poor solubility, low tumor selectivity, and suboptimal photostability. This review critically examines purpurin-18 and related chlorin-based nanocarriers as next-generation photosensitizer systems for PDT. Although their names are similar, purpurin-18 is chemically distinct from natural anthraquinone purpurin and is classified as a chlorin-type tetrapyrrolic macrocycle. Due to its red-light absorption, ROS-generating capacity, and chemical modifiability, purpurin-18 has shown improved therapeutic potential when incorporated into nanocarrier systems. Nanocarrier engineering significantly improves photosensitizer dispersibility, stability, and tumor targeting, enabling enhanced intracellular uptake and apoptosis induction across multiple cancer models. Despite promising preclinical outcomes, challenges related to safety, biodistribution, standardized photophysical characterization, and clinical translation persist. Future directions include the development of stimuli-responsive systems, combinatorial therapeutic strategies, and AI-assisted nanocarrier optimization to advance purpurin-18-based nano-PDT toward clinical applicability.