Surface Engineering of Escherichia coli–Derived OMVs as Promising Nano-Carriers to Target EGFR-Overexpressing Breast Cancer Cells

Bacterial outer membrane vesicles (OMVs) have recently drawn a great deal of attention due to their therapeutic efficiency and ability to target specific cells. In the present study, we sought to probe engineered OMVs as novel and promising carriers to target breast cancer cells. Following the fusio...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Zahra Sepahdar, Mehran Miroliaei, Saeid Bouzari, Vahid Khalaj, Mona Salimi
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	outer membrane vesicles epidermal growth factor receptor breast cancer engineering affibody Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/d5ad65a142794032bbec6137fa0e368e
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:d5ad65a142794032bbec6137fa0e368e
record_format	dspace
spelling	oai:doaj.org-article:d5ad65a142794032bbec6137fa0e368e2021-11-18T17:09:19ZSurface Engineering of Escherichia coli–Derived OMVs as Promising Nano-Carriers to Target EGFR-Overexpressing Breast Cancer Cells1663-981210.3389/fphar.2021.719289https://doaj.org/article/d5ad65a142794032bbec6137fa0e368e2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.719289/fullhttps://doaj.org/toc/1663-9812Bacterial outer membrane vesicles (OMVs) have recently drawn a great deal of attention due to their therapeutic efficiency and ability to target specific cells. In the present study, we sought to probe engineered OMVs as novel and promising carriers to target breast cancer cells. Following the fusion of the affiEGFR-GALA structure to the C-terminal of ClyA as an anchor protein, the ClyA-affiEGFR-GALA construct was successfully expressed on the surface of ∆msbB/∆pagP E. coli W3110-derived OMVs. Morphological features of the engineered and wild-type OMVs were identical. The engineered OMVs induced no endotoxicity, cytotoxicity, or immunogenicity, indicating the safety of their application. These OMVs could specifically bind to EGF receptors of MDA-MB-468 cells expressing high levels of EGFR and not to those with low levels of EGFR (HEK293T cells). Interestingly, despite a lower binding affinity of the engineered OMVs relative to the positive control Cetuximab, it was strong enough to identify these cells. Moreover, confocal microscopy revealed no uptake of the modified OMVs by the EGFR-overexpressing cells in the presence of EGFR competitors. These results suggest that OMVs might internalize into the cells with EGF receptors, as no OMVs entered the cells with any EGFR expression or those pretreated with EGF or Cetuximab. Regarding the EGFR-binding affinity of the engineered OMVs and their cellular uptake, they are presented here as a potential carrier for cell-specific drug delivery to treat a wide variety of cancer cells. Interestingly, the engineered OMVs are capable of reaching the cytoplasm while escaping the endosome due to the incorporation of a fusogenic GALA peptide in the construct.Zahra SepahdarMehran MiroliaeiSaeid BouzariVahid KhalajMona SalimiFrontiers Media S.A.articleouter membrane vesiclesepidermal growth factor receptorbreast cancerengineeringaffibodyTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	outer membrane vesicles epidermal growth factor receptor breast cancer engineering affibody Therapeutics. Pharmacology RM1-950
spellingShingle	outer membrane vesicles epidermal growth factor receptor breast cancer engineering affibody Therapeutics. Pharmacology RM1-950 Zahra Sepahdar Mehran Miroliaei Saeid Bouzari Vahid Khalaj Mona Salimi Surface Engineering of Escherichia coli–Derived OMVs as Promising Nano-Carriers to Target EGFR-Overexpressing Breast Cancer Cells
description	Bacterial outer membrane vesicles (OMVs) have recently drawn a great deal of attention due to their therapeutic efficiency and ability to target specific cells. In the present study, we sought to probe engineered OMVs as novel and promising carriers to target breast cancer cells. Following the fusion of the affiEGFR-GALA structure to the C-terminal of ClyA as an anchor protein, the ClyA-affiEGFR-GALA construct was successfully expressed on the surface of ∆msbB/∆pagP E. coli W3110-derived OMVs. Morphological features of the engineered and wild-type OMVs were identical. The engineered OMVs induced no endotoxicity, cytotoxicity, or immunogenicity, indicating the safety of their application. These OMVs could specifically bind to EGF receptors of MDA-MB-468 cells expressing high levels of EGFR and not to those with low levels of EGFR (HEK293T cells). Interestingly, despite a lower binding affinity of the engineered OMVs relative to the positive control Cetuximab, it was strong enough to identify these cells. Moreover, confocal microscopy revealed no uptake of the modified OMVs by the EGFR-overexpressing cells in the presence of EGFR competitors. These results suggest that OMVs might internalize into the cells with EGF receptors, as no OMVs entered the cells with any EGFR expression or those pretreated with EGF or Cetuximab. Regarding the EGFR-binding affinity of the engineered OMVs and their cellular uptake, they are presented here as a potential carrier for cell-specific drug delivery to treat a wide variety of cancer cells. Interestingly, the engineered OMVs are capable of reaching the cytoplasm while escaping the endosome due to the incorporation of a fusogenic GALA peptide in the construct.
format	article
author	Zahra Sepahdar Mehran Miroliaei Saeid Bouzari Vahid Khalaj Mona Salimi
author_facet	Zahra Sepahdar Mehran Miroliaei Saeid Bouzari Vahid Khalaj Mona Salimi
author_sort	Zahra Sepahdar
title	Surface Engineering of Escherichia coli–Derived OMVs as Promising Nano-Carriers to Target EGFR-Overexpressing Breast Cancer Cells
title_short	Surface Engineering of Escherichia coli–Derived OMVs as Promising Nano-Carriers to Target EGFR-Overexpressing Breast Cancer Cells
title_full	Surface Engineering of Escherichia coli–Derived OMVs as Promising Nano-Carriers to Target EGFR-Overexpressing Breast Cancer Cells
title_fullStr	Surface Engineering of Escherichia coli–Derived OMVs as Promising Nano-Carriers to Target EGFR-Overexpressing Breast Cancer Cells
title_full_unstemmed	Surface Engineering of Escherichia coli–Derived OMVs as Promising Nano-Carriers to Target EGFR-Overexpressing Breast Cancer Cells
title_sort	surface engineering of escherichia coli–derived omvs as promising nano-carriers to target egfr-overexpressing breast cancer cells
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/d5ad65a142794032bbec6137fa0e368e
work_keys_str_mv	AT zahrasepahdar surfaceengineeringofescherichiacoliderivedomvsaspromisingnanocarrierstotargetegfroverexpressingbreastcancercells AT mehranmiroliaei surfaceengineeringofescherichiacoliderivedomvsaspromisingnanocarrierstotargetegfroverexpressingbreastcancercells AT saeidbouzari surfaceengineeringofescherichiacoliderivedomvsaspromisingnanocarrierstotargetegfroverexpressingbreastcancercells AT vahidkhalaj surfaceengineeringofescherichiacoliderivedomvsaspromisingnanocarrierstotargetegfroverexpressingbreastcancercells AT monasalimi surfaceengineeringofescherichiacoliderivedomvsaspromisingnanocarrierstotargetegfroverexpressingbreastcancercells
_version_	1718420814717517824

Surface Engineering of Escherichia coli–Derived OMVs as Promising Nano-Carriers to Target EGFR-Overexpressing Breast Cancer Cells

Ejemplares similares