Nitric Oxide-propelled Nanomotors For Bacterial Biofilm Elimination And Endotoxin Removal To Treat Infected Burn Wounds

Biofilm infection is regarded as a major adverse factor to treat the burn.Due to the protection of EPS,chemotherapy agents cannot penetrate effectively into the biofilm and lead to the failure of antibacterial treatment.Additionally,lipopolysaccharide（LPS）endotoxins on the surface of Gram-negative bacteria could be released out during bacterial division,after bacterial death,or under antibacterial treatment.LPS can induce the persistent wound inflammatory state,which in turn leads to healing delays and the formation of chronic wounds.Thus,it is necessary to design effective methods to promote the deep penetration into biofilms,bacteria destruction and LPS removal.Herein,Janus nanoparticles were prepared through partially coating Fe₃O₄ NPs with polydopamine（PDA）layers,and then polymyxin B（PMB）and thilolated nitric oxide（NO）donors were separately grafted on the Janus NPs to obtain IO@PMB-SNO nanomotors（NMs）.In response to elevated glutathione（GSH）in biofilms,NO gas generated from one side of Janus NMs leads to self-propelled motion and propel deep infiltration into biofilms.The local release of NO could promote the destruction of biofilms and the embedded bacteria,which provides a non-antibiotic antibacterial approach without generation of drug resistance.In addition to the intrinsic antibacterial effect,PMB grafts could preferentially bind with bacteria and the self-propelled motion enhances the LPS clearance and then significantly attenuates the production of inflammatory cytokines and reactive oxide species by macrophages.Partial-thickness burn wounds are established on mice and infected by P.aeruginosa,and the NMs treatment almost fully destructs bacteria in the wounds.IO@PMB-SNO NMs remove LPS from the wounds under a magnetic field and then downregulate interleukin-6 and tumor necrosis factor-αlevels in tissues.The infected wounds are completely healed with deposition of aligned collagen and generation of skin accessories similar to those of normal skin.Thus,IO@PMB-SNO NMs have achieved multiple-mode effects including GSH-triggered NO release and self-propelled motion,NO-afforded non-antibiotic elimination of biofilms and bacteria,and PMB-induced endotoxin removal.In summary,this study offers a feasible strategy with integral antibiofilm and anti-inflammatory effects to accelerate the healing of infected burn wounds.