Nanoparticles drug delivery for 5-aminolevulinic acid (5-ALA) in photodynamic therapy (PDT) for multiple cancer treatment: a critical review on biosynthesis, detection, and therapeutic applications

Photodynamic therapy (PDT) is a promising cancer treatment that kills cancer cells selectively by stimulating reactive oxygen species generation with photosensitizers exposed to specific light wavelengths. 5-aminolevulinic acid (5-ALA) is a widely used photosensitizer. However, its limited tumour penetration and targeting reduce its therapeutic efficacy. Scholars have investigated nano-delivery techniques to improve 5-ALA administration and efficacy in PDT. This review summarises recent advances in biological host biosynthetic pathways and regulatory mechanisms for 5-ALA production. The review also highlights the potential therapeutic efficacy of various 5-ALA nano-delivery modalities, such as nanoparticles, liposomes, and gels, in treating various cancers. Although promising, 5-ALA nano-delivery methods face challenges that could impair targeting and efficacy. To determine their safety and biocompatibility, extensive preclinical and clinical studies are required. This study highlights the potential of 5-ALA-NDSs to improve PDT for cancer treatment, as well as the need for additional research to overcome barriers and improve medical outcomes. Graphical abstract