Hypocrellin-Mediated PDT: A Systematic Review of Its Efficacy, Applications, and Outcomes.

Photodynamic therapy (PDT) is a light-activated treatment that generates reactive oxygen species (ROS) to induce microbial cell death. As resistance to traditional antibiotics intensifies globally, PDT has emerged as a promising alternative or adjunctive antimicrobial strategy. Among various photosensitizers, Hypocrellin, a perylenequinone compound, has shown high ROS yield and broad-spectrum activity against bacteria and fungi. This systematic review evaluated the efficacy, safety, and therapeutic potential of Hypocrellin-mediated antimicrobial photodynamic therapy. Following PRISMA 2020 guidelines, a comprehensive literature search was conducted in PubMed, Embase, Scopus, and the Cochrane Library for studies published between 2015 and 2025. Eligible studies included in vitro and preclinical in vivo research using Hypocrellin as a photosensitizer. Quality and risk of bias were assessed using a structured nine-item checklist. Ten eligible studies, all conducted in China, were included. Hypocrellin-mediated aPDT significantly reduced microbial loads in both planktonic and biofilm states of resistant pathogens such as Candida albicans, Candida auris, Cutibacterium acnes, and Staphylococcus aureus. The treatment acted via ROS-mediated apoptosis, membrane disruption, and mitochondrial dysfunction, with minimal cytotoxicity to mammalian cells. Studies also reported enhanced efficacy when Hypocrellin was incorporated into nanocarriers, polymeric scaffolds, or combined with chemodynamic or photothermal therapies. However, substantial heterogeneity was observed in Hypocrellin concentrations, irradiation parameters, and outcome measures. Hypocrellin-based PDT exhibits potent antimicrobial activity and favorable safety in preclinical settings, supporting its potential as an alternative to conventional antibiotics. However, standardized treatment protocols and robust clinical trials are urgently needed to validate long-term safety and translational feasibility. These findings underscore the broader promise of PDT in addressing drug-resistant infections through a mechanism unlikely to induce resistance.