Porphyrins and Their Derivatives in Cancer Therapy: Current Advances, Mechanistic Insights, and Prospective Directions

Porphyrin and its derivatives are widely used in cancer therapy due to their strong photon absorption capabilities and moderate light stability. Due to their hydrophobic nature, porphyrins with tetrapyrrolic macrocycles ease self-aggregation in physiological conditions. Instead, exploiting the C4 symmetry structure for self-assembly is beneficial to improve the bioavailability of porphyrin and its derivatives. Herein, this Review outlines porphyrin-based nanoformulations for therapeutic applications in cancer treatment. The typical pharmaceutical application of the integrated porphyrinic structure is systematically summarized, focusing on the typical synthetic methodologies and structure-functionality relationship. Additionally, therapeutic modalities (e.g., photothermal, photodynamic, and sonodynamic) and their synergy mechanism in regulated cell death are overviewed. Special attention is given to emerging technologies in nanocatalytic therapy, therapeutic vaccines, and proteolysis-targeting chimeras, which align with the trend toward personalization and minimal invasiveness in healthcare. Finally, we discuss the challenges and limitations of porphyrinic nanoformulations and explore their future directions in the healthcare sector, aiming to bridge the gap between research and practical clinical application.