Reactive Metal Boride Nanoparticles Trap Lipopolysaccharide and Peptidoglycan for Bacteria-Infected Wound Healing

Antibacterial wound healing approaches often target bacteria but overlook the inflammation response caused by products released by dead bacteria. The authors develop MB nanoparticles to prevent both infection and excessive inflammation by trapping the key component of bacteria, LPS/PGN.
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Impaired wound healing is a growing global concern driven by aging populations and the increasing prevalence of chronic conditions, such as diabetes and obesity. Infection is a major factor that delays wound healing, which can lead to sepsis and multiorgan failure, and even cause death in severe cases1, 2. Currently, antimicrobials such as antibiotics are used to treat infected wounds, however, the dead bacteria accumulating at the site of infection could induce undesirable tissue inflammation3, 4. The dead bacteria can release massive amounts of toxins (Lipopolysaccharide(LPS) in Gram-negative bacteria) and ( Peptidoglycan (PGN) in Gram-positive bacteria) that can activate immune cells to induce excessive inflammation and toxicity, leading to chronic and impaired wound healing5-8 (Figure 1). Therefore, developing strategies to simultaneously inhibit the survival of live bacteria and dead bacteria-induced excessive inflammation to heal infected wounds is urgently needed.

Figure 1. Both live and dead bacteria impair wound healing

LPS/PGN is a structural component of the bacteria cell wall, which maintains the integrity of the bacteria and protects the bacteria against antibacterial treatments. On the other hand, LPS/PGN is the main functional component of the endotoxin, which is released from the bacterial surface upon bacteria die or lyse. (People usually regard LPS as the endotoxin, in this manuscript, we regard both the dead bacteria-released LPS and PGN as the endotoxin) These free LPS/PGN can induce excessive inflammation and toxicity to the host. Therefore, targeting the key component of bacteria (LPS/PGN) may simultaneously inhibit bacterial survival and dead bacteria-induced excessive inflammation.

The dynamic borate ester bonds are widely used to identify glucose through the esterification reaction between boron dihydroxy group and 1,2-diol or 1,3-dial dihydroxyl groups of glucose9-11. Therefore, materials possessing boron dihydroxyl functional groups may react with LPS/PGN, as they also contain structures of 1,2-diol or 1,3-diol. However, such dynamic covalent bonds easily dissociate under acidic and inflammatory conditions. Hence, it is extremely necessary to design an antibacterial reagent that efficiently forms stable borate ester bonds with the key component of bacterial LPS/PGN, finally promoting wound healing.

Herein, we proposed a boron-trapping strategy and synthesized a class of nano-scale MB NPs (M=Mg, Al, and Be), using Nano-MgB2 as a representative example to elucidate the mechanism and function of MBs in promoting infected wound healing. The Nano-MgB2 are gradually hydrolyzed to generate boron dihydroxy groups and metal cations while generating a local alkaline microenvironment. This microenvironment greatly enhances boron dihydroxy groups to trap LPS or PGN through an esterification reaction, which not only enhanced metal cation-induced bacterial death but also inhibited dead bacteria-induced excessive inflammation both in vitro and in vivo, finally accelerating wound healing (Figure 2). Taken together, this boron-trapping strategy provides a new approach to the treatment of bacterial infection and the accompanying inflammation. The paper was published on Nature communications (Article link). 

Figure 2 Reactive metal borides (such as Nano-MgB2) were gradually hydrolyzed to generate boron dihydroxy groups (HO-B-OH) and a local alkaline microenvironment. The alkaline microenvironment promoted the HO-B-OH to trap the key component of bacteria (LPS/PGN) by forming a stable borate ester bond. The trapping of LPS/PGN not only inhibited the survival of live bacteria, but also blocked the excessive inflammatory response of immune cells, resulting in enhanced wound healing.
Figure 2. Boron-trapping strategy promotes wound healing

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