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

Author:

Ibrahim Usri H.1,Gafar Mohammed A.2,Khan Rene3,Tageldin Abdelrahman2,Govender Thirumala2,Mackraj Irene1ORCID

Affiliation:

1. Discipline of Human Physiology, School of Laboratory Medicine and Medical Sciences, College of Health Sciences University of KwaZulu‐Natal Durban South Africa

2. Discipline of Pharmaceutical Sciences, College of Health Sciences University of KwaZulu‐Natal Durban South Africa

3. Discipline of Medical Biochemistry, School of Laboratory Medicine and Medical Science University of KwaZulu‐Natal Durban South Africa

Abstract

AbstractAlarming 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.

Funder

College of Health Sciences, University of KwaZulu-Natal

Publisher

Wiley

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