Human Cell‐Camouflaged Nanomagnetic Scavengers Restore Immune Homeostasis in a Rodent Model with Bacteremia

• Published in: Small (Weinheim an der Bergstrasse, Germany) Vol. 18; no. 40; pp. e2203746 - n/a
• Main Authors: Park, Sung Jin, Kwon, Seyong, Lee, Min Seok, Jang, Bong Hwan, Guzmán‐Cedillo, Axel E., Kang, Joo H.
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley Subscription Services, Inc 01.10.2022
• Subjects: AMR; Blood; cell‐camouflaged nanomagnetic scavenger; Circuits; Coliforms; Combinatorial analysis; Cytokines; E coli; Endotoxins; Erythrocytes; extracorporeal blood‐cleansing treatment; Homeostasis; immune homeostasis; Leukocytes; Nanoparticles; Nanotechnology; Pathogens; SARS‐CoV‐2; Vancomycin; Viral diseases
• ISSN: 1613-6810; 1613-6829
• DOI: 10.1002/smll.202203746

Bloodstream infection caused by antimicrobial resistance pathogens is a global concern because it is difficult to treat with conventional therapy. Here, scavenger magnetic nanoparticles enveloped by nanovesicles derived from blood cells (MNVs) are reported, which magnetically eradicate an extreme range of pathogens in an extracorporeal circuit. It is quantitatively revealed that glycophorin A and complement receptor (CR) 1 on red blood cell (RBC)‐MNVs predominantly capture human fecal bacteria, carbapenem‐resistant (CR) Escherichia  coli, and extended‐spectrum beta‐lactamases‐positive (ESBL‐positive) E. coli, vancomycin‐intermediate Staphylococcus aureus (VISA), endotoxins, and proinflammatory cytokines in human blood. Additionally, CR3 and CR1 on white blood cell‐MNVs mainly contribute to depleting the virus envelope proteins of Zika, SARS‐CoV‐2, and their variants in human blood. Supplementing opsonins into the blood significantly augments the pathogen removal efficiency due to its combinatorial interactions between pathogens and CR1 and CR3 on MNVs. The extracorporeal blood cleansing enables full recovery of lethally infected rodent animals within 7 days by treating them twice in series. It is also validated that parameters reflecting immune homeostasis, such as blood cell counts, cytokine levels, and transcriptomics changes, are restored in blood of the fatally infected rats after treatment. Magnetic nanovesicles (MNVs) camouflaged with blood cell membranes are designed to capture an extensive range of inflammation‐triggering reagents via the interplays between opsonins in the blood and surface receptors of blood cells coated on MNVs. The extracorporeal blood‐cleansing treatment using MNVs fully recovers the lethally infected rodent animals and restores their immune homeostasis by eradicating pan‐inflammatory reagents in the blood.