Gallium–Carbenicillin Framework Coated Defect‐Rich Hollow TiO₂ as a Photocatalyzed Oxidative Stress Amplifier against Complex Infections

Abstract

Development of new strategies with high antimicrobial capability against complex bacterial infections is still challenging. Herein, a three-in-one synergistic antimicrobial platform is presented based on gallium-carbenicillin framework coated defect-rich hollow TiO 2 nanoshells (H-TiO 2−x @MOF), for simultaneous eradicating methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (PA) in complex infections, which are the two most common bacteria in wounds. The metal gallium can disrupt bacterial antioxidation system using a "Trojan horse" strategy by substituting iron in the antioxidant enzymes, and finally increase bacterial susceptibility to oxidants. Meanwhile, oxygen-deficient hollow TiO 2−x nanoshells (H-TiO 2−x NSs) can efficiently bind to the bacteria and promote local generation of abundant reactive oxygen species (ROS) under visible-light irradiation. Thus, the combination of gallium (antioxidant enzyme inhibitor) and black H-TiO 2−x NSs (ROS generator) constitutes a photocatalyzed oxidative stress amplifier that can boost ROS accumulation to destroy pathogens thoroughly. In addition, carbenicillin (Car), as the organic ligand coordinated to gallium ion, also acts as a broad-spectrum antibacterial agent against PA and shares the responsibility for combating complex infections simultaneously. In view of the superior antibacterial ability, accelerated healing of infected wounds, and good biosafety, the H-TiO 2−x @MOF potentially provides an alternative antibacterial agent to combat complex bacterial infections.

Antimicrobial TiO2 nanocomposite coatings for surfaces, dental and orthopaedic implants

“…A potential three-in-one antimicrobial platform was developed on a gallium (Ga)-carbenicillin (Car) framework coated with oxygen-deficient hollow TiO 2 nano-shells (H-TiO 2-x @MOF) to fight against methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (PA) under visible light irradiation [21] . The oxygen vacancies have proved to narrow the bandgap of TiO 2 , improving its optical absorption range towards visible and near-infrared (IR) regions.…”

“…In addition, the rough spiky surface of H-TiO 2-x could improve the adhesion of bacteria and on-site ROSs generation.

Figure 6 In-vivo studies of wound healing using various materials (Car, Ga, H-TiO 2-x @MOF): (A) schematic of experimental procedure, (B) photographs of the infected wounds at various time intervals, (C) survival rates for 14 days treatment, (D) quantitative representation of the infection percentage at various time intervals, (E) H and E stained images of the tissue sections at 7 and 14 days, and (F) photographs of plated bacterial colonies from the infected skin tissues [21] . Reproduced with permission from [21] .

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“…TiO 2 is one of the broad-spectrum bactericides with self-sterilizing effects and it could reduce the number of adhered microbes through increasing the electron donor surface energy of the coating [15] , [16] , [17] , [18] . In most of the recent studies, TiO 2 has been doped with metals/non-metals or other chemical modifiers to extend the light absorption into the visible region and improve the photo-generated charge transfer process [19] , [20] , [21] , [22] .…”

Recent near-infrared light-activated nanomedicine toward precision cancer therapy

“…1 Over the past few decades, optical manipulation also ignited greater interest for applications in the medical field including local diagnosis, in vivo imaging, and phototherapy due to its minimal invasion and high spatiotemporal selectivity. [2][3][4][5][6] In particular, the exploration of near-infrared (NIR) light in biological applications is gaining strong momentum, and more than 3000 achievements regarding NIR phototherapy were found in the past three years (Fig. 1A).…”

Gallium (Ga)–strontium (Sr) layered double hydroxide composite coating on titanium substrates for enhanced osteogenic and antibacterial abilities

“…Gallium nitrate (Ga(NO 3 ) 3 ) was approved by the Food and Drug Administration (FDA) and is widely applied as an effective anti‐hypercalcemia and malignancy drug 11,12 . Ga(NO 3 ) 3 also has broad antimicrobial properties against methicillin‐resistant Staphylococcus aureus (MRSA), Escherichia coli ( E. coli ), S. aureus , and Pseudomonas aeruginosa 13,14 . Previous studies have confirmed that iron ions (Fe 3+ ) participate in survival of most microorganisms and the metabolic process of proteins and DNA synthesis, electron transfer, respiration, and oxidative stress defense 15‐17 .…”