Antibacterial Sonodynamic Therapy: Current Status and Future Perspectives

Abstract

Multidrug-resistant bacteria have emerged in both community and hospital settings, partly due to the misuse of antibiotics. The inventory of viable antibiotics is rapidly declining, and efforts toward discovering newer antibiotics are not yielding the desired outcomes. Therefore, alternate antibacterial therapies based on physical mechanisms such as light and ultrasound are being explored. Sonodynamic therapy (SDT) is an emerging therapeutic approach that involves exposing target tissues to a nontoxic sensitizing chemical and low-intensity ultrasound. SDT can enable site-specific cytotoxicity by producing reactive oxygen species (ROS) in response to ultrasound, which can be harnessed for treating bacterial infections. This approach can potentially be used for both superficial and deep-seated microbial infections. The majority of the sonosensitizers reported are nonpolar, exhibiting limited bioavailability and a high clearance rate in the body. Therefore, targeted delivery agents such as nanoparticle composites, liposomes, and microbubbles are being investigated. This article reviews recent developments in antibacterial sonodynamic therapy, emphasizing biophysical and chemical mechanisms, novel delivery agents, ultrasound exposure and image guidance strategies, and the challenges in the pathway to clinical translation.

Applications of Antimicrobial Photodynamic Therapy against Bacterial Biofilms

“…Sonodynamic therapy (SDT) is an innovative combination of PDT and ultrasound that involves exposing diseased tissues to chemical compounds that produce reactive oxygen species upon sensitization by means of low-intensity ultrasound. In addition to the reported anticancer research applications [ 146 ], it has been applied to antimicrobial research studies with promising results in vitro [ 147 , 148 , 149 ]. The evaluation of SDT may be illustrated with the comparison between PDT and SDT for Staphylococcus aureus biofilm samples [ 150 ].…”

Recent developments of sonodynamic therapy in antibacterial application

“…infections. 3 In addition, most bacteria in nature live as biofilms. As highly structured surface microorganisms, biofilms could boost bacterial resistance with 10-1000 times the necessary antibiotic dose than the planktonic form.…”

“…As highly structured surface microorganisms, biofilms could boost bacterial resistance with 10-1000 times the necessary antibiotic dose than the planktonic form. 3,4 Furthermore, bacteria in biofilms could enhance bacterial virulence through population-sensing molecular interactions. 5 In 2019, a report from the United Nations stated that drug-resistant bacterial infections killed at least 700 000 people globally each year.…”

“…[22][23][24] Furthermore, US causes cavitation and increases biofilm fluidity, promoting the absorption of sonosensitizers and providing benefits for anti-biofilm treatment. 3 In addition, US has the advantages of real time, low cost and no ionizing radiation, 23,25 shedding new light to cure drugresistant bacterial infection.…”

“…In recent years, the increasing use of antibiotics caused the evolution of many drug-resistant strains, resulting in a considerable rise in the minimum antibiotic concentration required to treat bacterial infections. 3 In addition, most bacteria in nature live as biofilms. As highly structured surface microorganisms, biofilms could boost bacterial resistance with 10–1000 times the necessary antibiotic dose than the planktonic form.…”