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 in vivo, 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.