Erythrocyte membrane-enveloped molybdenum disulfide nanodots for biofilm elimination on implants via toxin neutralization and immune modulation

• Published in: Journal of materials chemistry. B, Materials for biology and medicine Materials for biology and medicine, 2022-03, Vol.10 (11), p.1805-1820
• Main Authors: Shi, Tingwang, Ruan, Zesong, Wang, Xin, Lian, Xiaofeng, Chen, Yunfeng
• Format: Article
• Language: English
• Subjects: Antiinfectives and antibacterials; Biofilms; Disulfides; Drug resistance; Erythrocyte Membrane; Erythrocytes; Fever; Hyperthermia; I.R. radiation; Immune clearance; Immunomodulation; Immunoregulation; Immunosuppression; Infections; Inflammation; Infrared lasers; Irradiation; Laser damage; Lasers; Macrophages; Membranes; Microenvironments; Molybdenum; Molybdenum - pharmacology; Molybdenum disulfide; Nanotubes; Neutralization; Peroxidase; Phenotypes; Pore formation; Radiation damage; Reactive Oxygen Species; Therapy; Toxins; Transplants & implants; Virulence
• ISSN: 2050-750X; 2050-7518
• DOI: 10.1039/d1tb02615a

Implant-related infections (IRIs) caused by bacterial biofilms remain a prevalent but tricky clinical issue, and are characterized by drug resistance, toxin impairment and immunosuppression. Recently, reactive oxygen species (ROS)- and hyperthermia-based antimicrobial therapies have been developed to effectively destroy biofilms. However, almost all of them have failed to simultaneously focus on the immunosuppressive biofilm microenvironment and bacterial toxin-induced tissue damage. Herein, we proposed a one-arrow-three-hawks strategy to orchestrate hyperthermia/ROS antibiofilm therapy, toxin neutralization and immunomodulatory therapy through engineering a bioinspired erythrocyte membrane-enveloped molybdenum disulfide nanodot (EM@MoS ) nanoplatform. In the biofilm microenvironment, pore-forming toxins actively attack the erythrocyte membranes on the nanodots and are detained, thus staying away from their targets and mitigating tissue damage. Under near-infrared (NIR) laser irradiation, MoS nanodots, with superb photothermal and peroxidase (POD)-like properties, exert a powerful synergistic antibiofilm effect. More intriguingly, we initially identified that they possessed the ability to reverse the immunosuppressive microenvironment by skewing the macrophages from an anti-inflammatory phenotype to a proinflammatory phenotype, which would promote the elimination of biofilm debris and prevent infection relapse. Systematic and evaluations have demonstrated that EM@MoS achieves a remarkable antibiofilm effect. The current study integrated the functions of hyperthermia/ROS therapy, virulence clearance and immune regulation, which could provide an effective paradigm for IRIs therapy.