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. 2024 Aug 23;3(8):e70000.
doi: 10.1002/jex2.70000. eCollection 2024 Aug.

Engineered extracellular vesicles coated with an antimicrobial peptide for advanced control of bacterial sepsis

Usri H Ibrahim  1 , Mohammed A Gafar  2 , Rene Khan  3 , Abdelrahman Tageldin  2 , Thirumala Govender  2 , Irene Mackraj  1
Affiliations

Engineered extracellular vesicles coated with an antimicrobial peptide for advanced control of bacterial sepsis

Usri H Ibrahim et al. J Extracell Biol. .

Abstract

Alarming sepsis-related mortality rates present significant challenges to healthcare services globally. Despite advances made in the field, there is still an urgent need to develop innovative approaches that could improve survival rates and reduce the overall cost of treatment for sepsis patients. Therefore, this study aimed to develop a novel multifunctional therapeutic agent for advanced control of bacterial sepsis. Extracellular vesicles (EVs) isolated from lipopolysaccharide (LPS) induced HepG2 (hepatocellular carcinoma cells) (iEV) displayed an average particle size of 171.63 ± 2.77 nm, a poly dispersion index (PDI) of 0.32 ± 0.0, and a zeta potential (ZP) of -11.87 ± 0.18 mV. Compared to HepG2 EV, LPS induction significantly increases the EV protein concentration, PDI and ZP, reduces the average size and promotes cell proliferation and cytoprotective effects of the isolated EVs (iEVs) against LPS-induced cytotoxicity. Coating of iEV with a cationic antimicrobial peptide (AMP) to form PC-iEV slightly changed their physical properties and shifted their surface charge toward neutral values. This modification improved the antibacterial activity (2-fold lower minimum bactericidal concentration [MBC] values) and biocompatibility of the conjugated peptide while maintaining iEV cytoprotective and anti-inflammatory activities. Our findings indicate the superior anti-inflammatory and antibacterial dual activity of PC-iEV against pathogens associated with sepsis.

Keywords: antimicrobial peptides: extracellular vesicles; sepsis; therapeutics.

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Conflict of interest statement

The authors declare that there is no conflict of interest.

Figures

FIGURE 1
FIGURE 1
TEM images for HepG2 iEVs isolated using the precipitation method (magnified at the bottom right). The image also illustrated lipoprotein aggregates co‐isolated with EVs (white circular particles). Scale bar: 100 nm.
FIGURE 2
FIGURE 2
TEM images for HepG2 EVs isolated using the precipitation method (magnified in the bottom right). The image also illustrated lipoprotein aggregates co‐isolated with EVs (white circular particles). Scale bar: 0.2 µm.
FIGURE 3
FIGURE 3
The effect of HepG2 EVs and LPS‐induced HepG2 EVs in the cell viability of (a) HepG2 cell line and (b) HEK 293 Cells. *p < 0.05 versus control (untreated cells), # p < 0.05 versus LPS 0.9 mg/mL, ∆ p < 0.05 versus respective concentration of HepG2 EVs. There were significant increases in cell viability of LPS‐induced HepG2 EVs‐treated groups compared to HepG2 EVs‐treated groups. Results were represented as mean ± standard deviation. The significance of differences was calculated using one‐way ANOVA test, n = 3.
FIGURE 4
FIGURE 4
Cytoprotective effect of LPS‐induced HepG2 EVs against LPS‐induced cytotoxicity on HepG2 cell line. * p < 0.05 versus control (untreated cells), # p < 0.05 versus LPS 0.9 mg/mL, ∆ p < 0.05 versus respective concentration of HepG2 EVs. Results were represented as mean ± standard deviation. The significance of differences was calculated using one‐way ANOVA test, n = 3.
FIGURE 5
FIGURE 5
TEM images for PC‐iEVs. The image also illustrated lipoprotein aggregates co‐isolated with EVs (white circular particles). Scale bar: 50 nm.
FIGURE 6
FIGURE 6
Cytoprotective effect of PC‐iEVs against LPS‐induced cytotoxicity and the effect of the AMP‐A on cell viability of HepG2 cell line. * p < 0.05 versus control (untreated cells), ∆ p < 0.05 versus LPS 0.9 mg/mL. Results were represented as mean ± standard deviation. The significance of differences was calculated using a one‐way ANOVA test, n = 3.
FIGURE 7
FIGURE 7
Anti‐inflammatory effect of PC‐iEVs against LPS‐induced inflammatory responses (a) TNF levels, (b) IL‐6 level among different treated groups. * p < 0.05 versus Control (untreated cells), ∆ p < 0.05 versus LPS 0.9 mg/mL. Results were represented as mean ± standard deviation. The significance of differences was calculated using one‐way ANOVA test, n = 3.
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References

    1. Abdel‐Aal, M. A. A. , Abdel‐Aziz, S. A. , Shaykoon, M. S. A. , & Abuo‐Rahma, G. E.‐D. A. (2019). Towards anticancer fluoroquinolones: A review article. Archiv Der Pharmazie, 352(7), 1800376. 10.1002/ardp.201800376 - DOI - PubMed
    1. Abdel‐Rahman, I. M. , Mustafa, M. , Mohamed, S. A. , Yahia, R. , Abdel‐Aziz, M. , Abuo‐Rahma, G. E.‐D. A. , & Hayallah, A. M. (2021). Novel Mannich bases of ciprofloxacin with improved physicochemical properties, antibacterial, anticancer activities and caspase‐3 mediated apoptosis. Bioorganic Chemistry, 107, 104629. 10.1016/j.bioorg.2021.104629 - DOI - PubMed
    1. Abou‐Yousef, H. , Dacrory, S. , Hasanin, M. , Saber, E. , & Kamel, S. (2021). Biocompatible hydrogel based on aldehyde‐functionalized cellulose and chitosan for potential control drug release. Sustainable Chemistry and Pharmacy, 21, 100419. 10.1016/j.scp.2021.100419 - DOI
    1. Ahadi, H. , Shokrzadeh, M. , Hosseini‐khah, Z. , Ghassemi barghi, N. , Ghasemian, M. , Emadi, E. , Zargari, M. , Razzaghi‐Asl, N. , & Emami, S. (2020). Synthesis and biological assessment of ciprofloxacin‐derived 1,3,4‐thiadiazoles as anticancer agents. Bioorganic Chemistry, 105, 104383. 10.1016/j.bioorg.2020.104383 - DOI - PubMed
    1. Alvarez, M. L. , Khosroheidari, M. , Ravi, R. K. , & DiStefano, J. K. (2012). Comparison of protein, microRNA, and mRNA yields using different methods of urinary exosome isolation for the discovery of kidney disease biomarkers. Kidney International, 82(9), 1024–1032. - PubMed

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