Advancing antimicrobial therapies: Phage-mediated phototherapeutic approaches – A systematic review

Background and Objective Bacteriophage (Phage) therapy offers targeted control of bacteria, while phototherapy exerts localised antimicrobial effects via oxidative or thermal mechanisms. Amid growing antimicrobial resistance and intolerance, combining these approaches may enhance efficacy and reduce treatment limitations. This systematic review aims to evaluate the current evidence on the combined use of phage therapy and phototherapy to control microbial infections. Methods A comprehensive literature search was conducted across databases for studies published up to April 2025. Eligible studies included in vitro, in vivo, and clinical research investigating the combined application of phages and phototherapy against microbial pathogens. The modified Critical Appraisal Skills Programme (CASP) Qualitative Checklist was used to assess the quality of the published study. Data were extracted and synthesised qualitatively. Results A total of seven studies met the inclusion criteria. All seven studies were preclinical investigations that demonstrated enhanced antimicrobial efficacy when phages were used in conjunction with visible light. Except for one, all six studies employed photosensitizers and followed a protocol in which phage induction was followed by light exposure. The observed synergistic effect was attributed to the combined properties of bacteriophages, photosensitizers, and light activation. Bacteriophages enabled targeted delivery of photosensitizers to bacterial cells and enhanced membrane permeability, facilitating greater intracellular uptake. Subsequent light activation increased reactive oxygen species (ROS) generation, thereby enhancing antimicrobial efficacy and bacterial killing. One study reported reductions of up to 4 log10 in bacterial load and demonstrated biofilm disruption with up to 98.7% eradication. Minimal or negligible cytotoxic effects were recorded with these approaches. Conclusions The integration of phage and phototherapy demonstrated considerable promise as an enhanced antimicrobial approach. This study concludes that the amalgamation of the specificity of phage for bacteria with light energy, mostly within the wavelength of the visible light spectrum, results in enhanced disruption of the microbial community in both planktonic and biofilm states. The studies included in this review also reflect on the safety of off-target cells and demonstrate limited cytotoxicity in preclinical models. While preclinical evidence is encouraging, further research, particularly clinical trials, is essential to validate efficacy, optimise protocols, and assess safety. This novel therapeutic approach may contribute to the next generation of antimicrobial treatments in the era of AMR.