Sono‐Immunotherapeutic Nanocapturer to Combat Multidrug‐Resistant Bacterial Infections

Abstract

Antibiotic‐free methods hold particular promise for preventing and controlling multidrug‐resistant (MDR) bacterial infection via eradiation of bacteria and their pathogenic virulence. A facile and bioinspired strategy is presented for bridging antibacterial sonodynamic therapy and antivirulence immunotherapy. As a proof‐of‐concept, an antibody which neutralizes alpha‐toxin of methicillin‐resistant Staphylococcus aureus (MRSA) is genetically engineered on to the surface of cell membrane nanovesicles, which then undergo sonosensitizer encapsulation. Compared with conventional passive virulence absorption using natural red blood membrane, the highly active antibody–toxin interaction enables the nanovesicles to capture virulence more potently in vitro. Upon ultrasound activation, the sonosensitizers efficiently generate reactive oxygen species to kill bacteria and accelerate the virulence clearance. In vivo optical imaging shows that the antibody‐piloted nanocapturer can successfully locate MRSA infection and accurately distinguish the foci from sterile inflammation. In situ magnetic resonance imaging and oxyhemoglobin saturation detection visualize the treatment progression, revealing a complete sono‐immunotherapeutic eradication of MRSA myositis in mice. The first combination of antibacterial sonodynamic therapy and antivirulence immunotherapy, which promises a new way for antibiotic‐free nanotheranostics to robustly combat MDR bacterial infections, is presented.

Ultrasound‐Activated Sensitizers and Applications

“…Similar to PDT, the production of a large amount of ROS induces cell apoptosis. US has been reported to induce oxidation, which has been proven by the bleaching of 9,10‐dimethylanthracene or the morphological change of cells . However, SDT does not only rely on ROS generation, other mechanisms have also gradually been discovered.…”

Leveraging metal oxide nanoparticles for bacteria tracing and eradicating

“…65,66 Compared with photo-induced antibacterial therapies that are limited to skin lesion, such sonodynamic therapy takes advantage of superior tissue penetrability of ultrasonic wave, showing great potential in deeply seated diseases. 67,13…”

“…12 For instance, the succeed application of genetically engineered cell membranederived nanovesicles effectively combined antibacterial sonodynamic therapy with antivirulence immunotherapy, resulting in a complete eradication of MDR bacterial infections. 13 Among all these newly discovered nanomaterials, the metal oxide nanoparticles play a crucial role in antimicrobial domains before the discovery of antibiotics in 1920. 14 These oxide nanoparticles possess greater durability, lower toxicity, and higher stability.…”

Ultraschallaktivierte Sensibilisatoren

“…Ähnlich der PDT induziert ein Großteil der produzierten ROS eine Zellapoptose. Es wurde berichtet, dass US die Oxidation induziert, was durch das Bleichen von 9,10‐Dimethylanthracen oder der morphologischen Veränderung von Zellen nachgewiesen wurde . SDT stützt sich jedoch nicht nur auf die Erzeugung von ROS.…”

“…Im Zuge neuer Innovationen in der Immuntherapie wurde auch über die Kombination mit SDT berichtet . Zhang et al.…”