Photocatalytic Quantum Dot‐Armed Bacteriophage for Combating Drug‐Resistant Bacterial Infection

• Published in: Advanced science 2022-06, Vol.9 (17), p.e2105668-n/a
• Main Authors: Wang, Lei, Fan, Xin, Gonzalez Moreno, Mercedes, Tkhilaishvili, Tamta, Du, Weijie, Zhang, Xianlong, Nie, Chuanxiong, Trampuz, Andrej, Haag, Rainer
• Format: Article
• Language: English
• Subjects: Animals; Anti-Bacterial Agents - pharmacology; Antibiotics; Bacteria; Bacterial infections; bacteriophage therapy; Bacteriophages; Biofilms; biofilm‐associated infection; Enzymes; functional antibacterial nanosystem; Infections; Light; Mice; Nanomaterials; Photocatalysis; photocatalytic therapy; Pseudomonas Infections - microbiology; Pseudomonas Infections - therapy; Quantum Dots; reactive oxygen species (ROS); Wound Infection
• ISSN: 2198-3844; 2198-3844
• DOI: 10.1002/advs.202105668

Multidrug‐resistant (MDR) bacterial infection is one of the greatest challenges to public health, a crisis demanding the next generation of highly effective antibacterial agents to specifically target MDR bacteria. Herein, a novel photocatalytic quantum dot (QD)‐armed bacteriophage (QD@Phage) is reported for combating green fluorescent protein‐expressing Pseudomonas aeruginosa (GFP‐P. aeruginosa) infection. The proposed QD@Phage nanosystem not only specifically binds to the host GFP‐P. aeruginosa while preserving the infectivity of the phage itself, but also shows a superior capacity for synergistic bacterial killing by phage and by the photocatalytic localized reactive oxygen species (ROS) generated from anchored QD components. Notably, this highly targeted QD@Phage nanosystem achieves robust in vitro antibacterial elimination for both planktonic (over 99.9%) and biofilm (over 99%) modes of growth. In a mouse wound infection model, this system also shows remarkable activity in eliminating the wound infection and promoting its recovery. These results demonstrate that the novel QD@Phage nanosystem can diversify the existing pool of antibacterial agents and inspire the development of promising therapeutic strategies against MDR bacterial infection. The proposed quantum dot‐armed bacteriophage (QD@Phage) can achieve robust bacterial elimination both in vitro and in vivo via phage‐assisted photocatalytic therapy (PA‐PCT). First, the nanosystem binds to the bacterial surface thanks to the preserved phage infectivity. Upon visible light irradiation, it can then locally generate singlet oxygen (1O2), thus synergistically achieving bactericidal efficacy.