Enhanced antimicrobial activity through the combination of antimicrobial photodynamic therapy and low-frequency ultrasonic irradiation.

The rapid increase of antibiotic resistance in pathogenic microorganisms has become one of the most severe threats to human health. Antimicrobial photodynamic therapy (aPDT), a light-based regimen, has offered a compelling nonpharmacological alternative to conventional antibiotics. The activity of aPDT is based on cytotoxic effect of reactive oxygen species (ROS), which are generated through the photosensitized reaction between photon, oxygen and photosensitizer. However, limited by the penetration of light and photosensitizers in human tissues and/or the infiltration of oxygen and photosensitizers in biofilms, the eradication of deeply located or biofilm-associated infections by aPDT remains challenging. Ultrasound irradiation bears a deeper penetration in human tissues than light and, sequentially, can promote drug delivery through cavitation effect. As such, the combination of ultrasound and aPDT represents a potent antimicrobial strategy. In this review, we summarized the recent progresses in the area of the combination therapy using ultrasound and aPDT, and discussed the potential mechanisms underlying enhanced antimicrobial effect by this combination therapy. The future research directions are also highlighted.