Novel nanoplatforms for antimicrobial photodynamic inactivation of bacterial biofilm infections

Biofilm-associated infections continue to pose a significant concern worldwide due to their inherent resistance to conventional antimicrobial agents and host immune defences. Antimicrobial photodynamic inactivation (aPDI) is a promising alternative to antibiotics, using photoactive molecules, photosensitisers (PSs), to produce cytotoxic reactive oxygen species (ROS) that destroy microbial cells. However, traditional PSs face challenges such as low solubility, limited biofilm penetration, and undesirable off-target toxicity, which limit their use in clinical settings. The utilisation of nanotechnology has revolutionised aPDI by overcoming these challenges, thereby enhancing PS solubility, stability, and intra-biofilm accumulation, while simultaneously enabling stimuli-responsive and actively targeted PS delivery. Various nanocarriers, such as polymeric, lipidic, inorganic, or hybrid types, have demonstrated significant potential to enhance ROS generation within the biofilm microenvironment and can be engineered to co-deliver antibiotics, chelators, DNase, or quorum-sensing inhibitors for synergistic antibacterial effects. The multifunctional systems also provide opportunities for photo-immunotherapeutic designs that combine ROS generation with immune stimulation. Although these developments have been successful, optimizing light dosimetry, PS quantum yields, biocompatibility, and large-scale translation remain significant challenges. Further progress in the development of mechanism-driven nanoplatforms and their standardization in clinical applications will be instrumental in establishing nano-aPDI as an effective treatment for resistant biofilm infections.