Endogenous stimuli-activatable photothermal therapy for bacterial infections

Photothermal therapy, a non-invasive treatment approach, has attracted growing attention in recent years for combating bacterial infections. When exposed to light, photothermal agents convert light energy into heat, generating localized hyperthermia that effectively eliminates infectious pathogens. However, hyperthermia-based treatments are prone to cause damage to the surrounding normal tissue. To enhance the antibacterial efficacy of photothermal therapy while minimizing side effects, researchers have developed activatable photothermal agents that respond to specific infection microenvironment triggers, such as acidic pH, elevated redox levels, and overexpressed enzymes. The specific physicochemical factors at the infection site modulate the activation of photothermal agent (on/off switching) or trigger auxiliary therapeutic modalities, simultaneously increasing bacterial susceptibility to photothermal treatment while optimizing biosafety and therapeutic specificity. Therefore, in this review, we first examined the current challenges in treating bacterial infections and elucidated the fundamental principles and advantages of photothermal antibacterial therapy. Then, the recent advancements (2020-2025) in activatable photothermal agents for anti-infection applications were summarized. Finally, we deliberated on the challenges and future development of activatable photothermal agents in anti-infective therapies. STATEMENT OF SIGNIFICANCE: Drug-resistant bacterial infections remain a major threat to human health, driving significant interest in photothermal antibacterial therapy. However, conventional photothermal treatments often rely on hyperthermia, which can indiscriminately damage surrounding healthy tissues. To maximize antibacterial efficacy while minimizing off-target effects, the development of smart photothermal agents responsive to infectious microenvironments has emerged as a critical research challenge. This review outlines key design strategies for stimuli-activated photothermal agents, highlights recent advances in the field, and discusses current limitations along with future prospects.