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Table 1 Summary of bioinspired synthetic EVs generated by cell fragmentation, supramolecular chemistry or biohybrid approaches, and inorganic NPs used in the context of sepsis

From: Bioengineered extracellular vesicles: future of precision medicine for sepsis

Starting material

Preparation method

Cargo

Particle characterization

Biological effect

Refs.

Bioinspired synthetic EVs

 Human promyelocytic leukemia HL-60 cells

Cell fragmentation: nitrogen cavitation + differential UC

TPCA-1

Size: ~ 200 nm (cryo-TEM)

ζ-potential: − 16 mV

Reduction of lung inflammation

[122]

 Human monocyte U397 cells

Cell fragmentation: alkaline solution + sonication + UC

Dexamethasone

Size: 130 nm (DLS)

Reduction of IL-8 levels and mitigation of SIRS

[121]

 MSCs

Cell fragmentation: serial extrusion (10, 5 and 1 μm) + DGUC

–

Size: 50–150 nm (TEM)

Decrease of inflammatory cytokines levels and immunomodulatory effect

[124]

 Polymers (HA, PEI)

Supramolecular chemistry: polymer coupling and self-assembly

miR-7651-5p, miR-615-5p, miR-6239, miR-690, miR-206-3p, miR-466i-5p and miR-146a-5p

Size: ~ 100 nm

Reduction of TNF-α and IL-6 levels and relief of LPS-induced sepsis

[127]

 Lipids (DPPC, DOPC, cholesterol) and membrane proteins from leukocytes

Supramolecular chemistry: mixing and assembly

–

Size: 94 nm (DLS)

ζ-potential: − 27 mV

Decrease of IL-6, IL-1b and TNF-α, rise of IL-10 and TGF-β, and prolongation of murine survival

[128]

 Amphotericin B-loaded liposomes

Commercial product

Amphotericin B

Size: 103 nm (DLS)

ζ-potential: − 54 mV

Identification of sepsis biomarkers for diagnosis purposes

[129]

 Polymer (Biotin-PEG-b-PAE(-g-PEG-b-DSPE)-b-PEG-Biotin)

Supramolecular chemistry: polymerization and self-assembly

Ciprofloxacin and TPCA-1

Size: 120 nm at pH = 7.4 (DLS)

Decrease in the number of leukocytes, bacteria and inflammatory cytokines, and mitigation of systemic inflammation

[130]

 Macrophage membrane + lipids (PC and DSPE-PEG2000)

Biohybrid strategy: stirring + sonication + extrusion (800, 400 and 200 nm)

–

Size: 203 nm (DLS)

ζ-potential: − 23 mV

Elimination of LPS and reduction of IL-1β, IL-6 and TNF-α levels

[134]

Inorganic NPs

 Fe3O4 NPs, chlorin e6 and aptamer

Fe3O4 NPs synthesis: thermal decomposition; EDC/NHS covalent coupling between Fe3O4 NPs, chlorin e6 and aptamer

–

Size: 17 nm (TEM)

ζ-potential: − 10 mV

Detection, death and separation of bacteria from contaminated blood

[136]

 Ceria NPs with mPEG-TK-PLGA coating

Ceria NPs synthesis: sol–gel; emulsion for polymer conjugation

Atorvastatin

Size: 43 nm (DLS)

ζ-potential: − 4 mV

Suppression of excessive ROS levels in mitochondria and reduction of inflammation

[137]

  1. EDC 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, DLS dynamic light scattering, DGUC density gradient ultracentrifugation, DOPC 1,2-dioleoyl-sn-glycero-3-phosphocholine, DPPC 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, DSPE 1,2-distearoyl-sn-glycero-3-phosphorylethanolamine, HA hyaluronic acid, LPS lipopolysaccharide, MSCs mesenchymal stem cells, NHS N-hydroxysuccinimide, PC phosphatidylcholine, PEG polyethylene glycol, PEI polyethylenimine, ROS reactive oxygen species, SIRS systemic inflammatory response syndrome, TK thioketal, TPCA-1 2-[(aminocarbonyl)amino]-5-(4-fluorophenyl)-3-thiophenecarboxamide, UC ultracentrifugation