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.

The synthesis of water-soluble thioglycosylated A2B2 type porphyrins and their zinc­(II) complexes is reported. The water-soluble trans-A2B2 porphyrins were synthesized in two steps, via [2+2] condensation between thioglycosylated dipyrromethanes and aromatic aldehydes in 15–21% yields. The thioglycosylated trans-A2B2 porphyrins showed decent in vitro singlet oxygen generation, which was supported by the intracellular DCFDA study. The in vitro cellular investigations of thioglycosylated A2B2 porphyrins were carried out in lung cancer cells (A549) to test their photodynamic therapeutic (PDT) activity. The PDT study revealed significant cytotoxicities of porphyrins with IC50 values between 23.3 and 44.2 μM in the dark, whereas, after visible light exposure, the photosensitizers exhibited IC50 values around 11.1–23.8 μM. The water-soluble thioglycosylated zinc­(II) porphyrins having two meso-N-butylcarbazole groups exhibited an excellent degree of photocytotoxicity (IC50 = 4.6–8.8 μM). The flow cytometry analysis revealed that cellular uptake and ROS (reactive oxygen species) generation efficiency of water-soluble thioglycosylated zinc­(II) porphyrins were considerably higher than nonmetalated porphyrins. Confocal microscopy images displayed substantial distribution in the endoplasmic reticulum with partial colocalization in mitochondria and lysosomes of water-soluble thioglycosylated zinc­(II) porphyrins in A549 cells.

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