Light-Activated Antimicrobial Agents and Biomaterials for Bacterial and Fungal Infections

Photodynamic therapy (PDT) represents a promising non-antibiotic strategy for addressing bacterial and fungal infections, particularly in the context of increasing antimicrobial resistance and biofilm-associated disease. PDT is based on the light-induced activation of photosensitizers, leading to the generation of reactive oxygen species (ROS), including singlet oxygen (1O2), which induce oxidative damage to multiple microbial targets. Unlike conventional antimicrobial drugs that often act through specific molecular pathways, antimicrobial PDT produces simultaneous damage to membranes, proteins, nucleic acids, and extracellular biofilm components, thereby reducing the probability of resistance development. This review critically analyzes the cellular, biochemical, and biophysical determinants that govern PDT selectivity toward bacterial and fungal cells in comparison with mammalian host tissues. Particular attention is given to photosensitizer localization, membrane interactions, photobleaching, oxygen dependence, light penetration, and the balance between Type I and Type II photochemical mechanisms. The review provides a comparative overview of major molecular photosensitizer classes, including phenothiazines, porphyrins, chlorins, phthalocyanines, xanthene dyes, natural polyphenols, endogenous compounds, and advanced targeted photosensitizers. In addition, this review distinguishes molecular photosensitizers from nanotechnology-based platforms and delivery systems. Nanoparticles, polymeric carriers, hydrogels, and light-activated coatings are discussed not only as photosensitizer delivery tools, but also as systems that modulate aggregation, improve localization, enhance biofilm penetration, and enable surface-confined ROS generation. ROS are capable of causing phototoxic effects wherever they are located. Unless selectively accumulated by target organisms, there can be systemic phototoxicity. Overall, PDT should be regarded as a modular antimicrobial platform in which photosensitizer chemistry, formulation, light delivery, oxygen availability, and infection biology must be co-optimized. Although further studies are required to address clinical translation, regulatory complexity, material safety, and standardized treatment protocols, PDT offers a scientifically robust and clinically relevant approach that may complement conventional antibacterial and antifungal therapies, especially in localized, biofilm-associated, and device-related infections.