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Human neutrophil membrane-derived nanovesicles as a drug delivery platform for improved therapy of infectious diseases.

ABSTRACT: Resolvins are a group of specialized proresolving lipid mediators (SPMs) enzymatically produced from omega-3 fatty acids during acute inflammation response to infections or tissue injury. Resolvin D1 (RvD1) is one of resolvins and is well studied in resolution of inflammation to treat inflammatory diseases. Resolution of inflammation includes the inhibition of polymorphonuclear leukocyte recruitment and reduced cytokine production. However, effective delivery of RvD1 to inflammatory tissues is challenging because of its lack of tissue targeting and poor physicochemical properties. Here, we proposed nanovesicles made from human neutrophil membrane which can specifically target inflamed tissues, and we loaded RvD1 on the surface of nanovesicles and antibiotic (ceftazidime, CEF) inside nanovesicles for improved treatment of bacterial infections. In a mouse model of bacterium-induced peritonitis, we demonstrated that human neutrophil cell membrane-formed vesicles (NMVs) enhanced inflammation resolution and bacterial killing after co-delivery of RvD1 and CEF. Our studies reveal that neutrophil nanovesicles may be critical for enhanced therapy to infectious diseases.

SUBMITTER: Gao J

PROVIDER: S-EPMC7920994 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Human neutrophil membrane-derived nanovesicles as a drug delivery platform for improved therapy of infectious diseases.

Gao Jin J Dong Xinyue X Su Yujie Y Wang Zhenjia Z

Acta biomaterialia 20210118

Resolvins are a group of specialized proresolving lipid mediators (SPMs) enzymatically produced from omega-3 fatty acids during acute inflammation response to infections or tissue injury. Resolvin D1 (RvD1) is one of resolvins and is well studied in resolution of inflammation to treat inflammatory diseases. Resolution of inflammation includes the inhibition of polymorphonuclear leukocyte recruitment and reduced cytokine production. However, effective delivery of RvD1 to inflammatory tissues is c ...[more]

PMID: 33476827

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Project description:Extracellular vesicles (EVs) have shown great promise as drug delivery system (DDS). However, their complex and costly production limit their development for clinical use. Interestingly, the plant kingdom can also produce EV-like nanovesicles that can easily be isolated and purified from a large quantity of raw material at a high yield. In this study, olive-derived nanovesicles (ODNVs) were isolated from raw fruits using serial centrifugations and their physical and biological features characterized to demonstrate their promising potential to be used as a DDS. Nanotracking particle analysis indicated an average size of 109.5 ± 3.0 nm and yield of 1012 ODNVs/mL for the purest fraction. Microscopy imaging, membrane fluidity assay and lipidomics analysis showed the presence of a rich lipid bilayer that significantly varied between different sources of ODNVs but showed a distinct signature compared to human EVs. Moreover, ODNVs were enriched in PEN1 and TET8 compared to raw fruits, suggesting an extracellular origin. Interestingly, ODNVs size and yield stayed unchanged after exposure to high temperature (70 °C for 1 h), wide pH range (5-10), and 50-100 nm extrusion, demonstrating high resistance to physical and chemical stresses. This high resistance allowed ODNVs to stay stable in water at 4 °C for a month, or with the addition of 25 mM trehalose for long-term freezing storage. Finally, ODNVs were internalized by both 2D and 3D cell culture without triggering significant cytotoxicity and immunogenicity. Importantly, the anticancer drug doxorubicin (dox) could be loaded by passive incubation within ODNVs and dox-loaded ODNVs decreased cell viability by 90% compared to only 70% for free dox at the same concentration, indicating a higher efficiency of drug delivery by ODNVs. In addition, this high cytotoxicity effect of dox-loaded ODNVs was shown to be stable after a 2-week storage at 4 °C. Together, these findings suggested that ODNVs represent a promising candidate as drug nanocarrier for various DDS clinical applications, as demonstrated by their biocompatibility, high resistance to stress, good stability in harsh environment, and improvement of anticancer drug efficacy.

Dataset Information

Human neutrophil membrane-derived nanovesicles as a drug delivery platform for improved therapy of infectious diseases.

Publications

Human neutrophil membrane-derived nanovesicles as a drug delivery platform for improved therapy of infectious diseases.

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