Sonoactivated Nanoantimicrobials: A Potent Armament in the Postantibiotic Era.

Recent research on antibiotic-free therapies has demonstrated remarkable effectiveness in preventing and controlling multi-drug-resistant (MDR) bacterial infection. Antimicrobial sonodynamic therapy (aSDT) developed from photodynamic therapy (PDT) is of particular interest to researchers and clinicians as it is a promising noninvasive treatment of less accessible infections. However, several aSDT-related challenges need to be addressed. These involve companion imaging and diagnosis of aSDT , insufficient efficacy of aSDT due to the limited oxygen level in the site of infection, infection in the immunocompromised host, and the synergetic approaches for enhanced ROS-mediated antimicrobial activity. This Spotlight on Applications presents the recent approaches in the development of sonoactivated nanoantimicrobials. These developed strategies including bacterial enzyme-responsive sonotheranostics, the ultrasound-switchable nanoenzyme-augmented aSDT, sono-immunomodulating therapy, and sonoactivated chemodynamic therapy (CDT) have shown positive outcomes in the treatment of MDR infections. However, despite the promising results of these approaches, a deeper understanding of the nanoantimicrobial SDT mechanisms in the more precise preclinical model is essential for future optimization regarding efficacy and safety.