Open Access

Scientific Reports, volume 11, issue 1, publication number 6489

Delivery of functional exogenous proteins by plant-derived vesicles to human cells in vitro

Garaeva Luiza ^{1, 2, 3}

Kamyshinsky Roman ^{1, 4, 5}

Kil Yury ^{2, 3, 6}

Varfolomeeva Elena ^{1, 3}

Verlov Nikolai ^{1, 3}

Komarova Elena ⁷

Garmay Yuri ³

Landa Sergey ³

Burdakov Vladimir ^{1, 3}

Myasnikov Alexander ³

Vinnikov Ilya A. ⁸

Margulis Boris ⁷

Guzhova Irina ⁷

Kagansky Alexander ^{5, 9}

Konevega Andrey L. ^{1, 2, 3}

Shtam Tatiana ^{1, 3, 7}

Hide authors affiliations Show authors affiliations: 9 affiliations

National Research Center “Kurchatov Institute”, Moscow, Russian Federation |

Peter The Great St. Petersburg Polytechnic University, St. Petersburg, Russian Federation |

Petersburg Nuclear Physics Institute named by B.P. Konstantinov of National Research Centre “Kurchatov Institute”, Gatchina, Russian Federation

National Research Centre "Kurchatov Institute"

Petersburg Nuclear Physics Institute of NRC «Kurchatov Institute»

⁴

Shubnikov Institute of Crystallography, Federal Scientific Research Centre ‘Crystallography and Photonics’, Russian Academy of Sciences, Moscow, Russian Federation

FSRC "Crystallography and photonics" of NRC «Kurchatov Institute»

Shubnikov Institute of Crystallography

⁵

Moscow Institute of Physics and Technology, Moscow, Russian Federation |

⁶

Kurchatov Genome Center-PNPI, Gatchina, Russian Federation

National Research Centre "Kurchatov Institute"

Petersburg Nuclear Physics Institute of NRC «Kurchatov Institute»

⁷

Institute of Cytology of Russian Academy of Sciences, St. Petersburg, Russian Federation |

⁸

Laboratory of Molecular Neurobiology, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China |

⁹

Center for Genomic and Regenerative Medicine, School of Biomedicine, Far Eastern Federal University, Vladivostok, Russian Federation |

Publication type: Journal Article

Publication date: 2021-03-22

Springer Nature

Journal: Scientific Reports

Quartile SCImago

Quartile WOS

Impact factor: 4.6

ISSN: 20452322

DOI: 10.1038/s41598-021-85833-y

Copy DOI

Multidisciplinary

Abstract

Plant-derived extracellular vesicles (EVs) gain more and more attention as promising carriers of exogenous bioactive molecules to the human cells. Derived from various edible sources, these EVs are remarkably biocompatible, biodegradable and highly abundant from plants. In this work, EVs from grapefruit juice were isolated by differential centrifugation followed by characterization of their size, quantity and morphology by nanoparticle tracking analysis, dynamic light scattering, atomic force microscopy and cryo-electron microscopy (Cryo-EM). In Cryo-EM experiments, we visualized grapefruit EVs with the average size of 41 ± 13 nm, confirmed their round-shaped morphology and estimated the thickness of their lipid bilayer as 5.3 ± 0.8 nm. Further, using cell culture models, we have successfully demonstrated that native grapefruit-derived extracellular vesicles (GF-EVs) are highly efficient carriers for the delivery of the exogenous Alexa Fluor 647 labeled bovine serum albumin (BSA) and heat shock protein 70 (HSP70) into both human peripheral blood mononuclear cells and colon cancer cells. Interestingly, loading to plant EVs significantly ameliorated the uptake of exogenous proteins by human cells compared to the same proteins without EVs. Most importantly, we have confirmed the functional activity of human recombinant HSP70 in the colon cancer cell culture upon delivery by GF-EVs. Analysis of the biodistribution of GF-EVs loaded with 125I-labeled BSA in mice demonstrated a significant uptake of the grapefruit-derived extracellular vesicles by the majority of organs. The results of our study indicate that native plant EVs might be safe and effective carriers of exogenous proteins into human cells.

By date By citations

Citations by journals

	1 2 3 4 5
International Journal of Molecular Sciences	International Journal of Molecular Sciences, 5, 9.09% International Journal of Molecular Sciences 5 publications, 9.09%
Pharmaceutics	Pharmaceutics, 3, 5.45% Pharmaceutics 3 publications, 5.45%
International Journal of Nanomedicine	International Journal of Nanomedicine, 3, 5.45% International Journal of Nanomedicine 3 publications, 5.45%
Biomedicines	Biomedicines, 2, 3.64% Biomedicines 2 publications, 3.64%
Frontiers in Cell and Developmental Biology	Frontiers in Cell and Developmental Biology, 2, 3.64% Frontiers in Cell and Developmental Biology 2 publications, 3.64%
Food and Function	Food and Function, 2, 3.64% Food and Function 2 publications, 3.64%
Open Research Europe	Open Research Europe, 1, 1.82% Open Research Europe 1 publication, 1.82%
Plants	Plants, 1, 1.82% Plants 1 publication, 1.82%
Nanomaterials	Nanomaterials, 1, 1.82% Nanomaterials 1 publication, 1.82%
Membranes	Membranes, 1, 1.82% Membranes 1 publication, 1.82%
Molecules	Molecules, 1, 1.82% Molecules 1 publication, 1.82%
Applied Sciences (Switzerland)	Applied Sciences (Switzerland), 1, 1.82% Applied Sciences (Switzerland) 1 publication, 1.82%
Frontiers in Cardiovascular Medicine	Frontiers in Cardiovascular Medicine, 1, 1.82% Frontiers in Cardiovascular Medicine 1 publication, 1.82%
Biocell	Biocell, 1, 1.82% Biocell 1 publication, 1.82%
Cell Communication and Signaling	Cell Communication and Signaling, 1, 1.82% Cell Communication and Signaling 1 publication, 1.82%
Fungal Biology and Biotechnology	Fungal Biology and Biotechnology, 1, 1.82% Fungal Biology and Biotechnology 1 publication, 1.82%
Scientific Reports	Scientific Reports, 1, 1.82% Scientific Reports 1 publication, 1.82%
Progress in Neurobiology	Progress in Neurobiology, 1, 1.82% Progress in Neurobiology 1 publication, 1.82%
Expert Opinion on Therapeutic Patents	Expert Opinion on Therapeutic Patents, 1, 1.82% Expert Opinion on Therapeutic Patents 1 publication, 1.82%
Journal of Nanobiotechnology	Journal of Nanobiotechnology, 1, 1.82% Journal of Nanobiotechnology 1 publication, 1.82%
Fundamental Research	Fundamental Research, 1, 1.82% Fundamental Research 1 publication, 1.82%
Seminars in Cancer Biology	Seminars in Cancer Biology, 1, 1.82% Seminars in Cancer Biology 1 publication, 1.82%
Pharmacology and Therapeutics	Pharmacology and Therapeutics, 1, 1.82% Pharmacology and Therapeutics 1 publication, 1.82%
Protein Expression and Purification	Protein Expression and Purification, 1, 1.82% Protein Expression and Purification 1 publication, 1.82%
Pharmaceutical Development and Technology	Pharmaceutical Development and Technology, 1, 1.82% Pharmaceutical Development and Technology 1 publication, 1.82%
Antioxidants	Antioxidants, 1, 1.82% Antioxidants 1 publication, 1.82%
Nutrients	Nutrients, 1, 1.82% Nutrients 1 publication, 1.82%
Journal of Phytopathology	Journal of Phytopathology, 1, 1.82% Journal of Phytopathology 1 publication, 1.82%
ChemistryOpen	ChemistryOpen, 1, 1.82% ChemistryOpen 1 publication, 1.82%

	1 2 3 4 5

Citations by publishers

	5 10 15 20
Multidisciplinary Digital Publishing Institute (MDPI)	Multidisciplinary Digital Publishing Institute (MDPI), 20, 36.36% Multidisciplinary Digital Publishing Institute (MDPI) 20 publications, 36.36%
Elsevier	Elsevier, 7, 12.73% Elsevier 7 publications, 12.73%
Springer Nature	Springer Nature, 6, 10.91% Springer Nature 6 publications, 10.91%
Frontiers Media S.A.	Frontiers Media S.A., 4, 7.27% Frontiers Media S.A. 4 publications, 7.27%
Royal Society of Chemistry (RSC)	Royal Society of Chemistry (RSC), 4, 7.27% Royal Society of Chemistry (RSC) 4 publications, 7.27%
Wiley	Wiley, 3, 5.45% Wiley 3 publications, 5.45%
Dove Medical Press	Dove Medical Press, 3, 5.45% Dove Medical Press 3 publications, 5.45%
Taylor & Francis	Taylor & Francis, 2, 3.64% Taylor & Francis 2 publications, 3.64%
F1000 Research	F1000 Research, 1, 1.82% F1000 Research 1 publication, 1.82%
Tech Science Press	Tech Science Press, 1, 1.82% Tech Science Press 1 publication, 1.82%
American Society of Plant Biologists	American Society of Plant Biologists, 1, 1.82% American Society of Plant Biologists 1 publication, 1.82%
Bentham Science	Bentham Science, 1, 1.82% Bentham Science 1 publication, 1.82%
	5 10 15 20

We do not take into account publications that without a DOI.
Statistics recalculated only for publications connected to researchers, organizations and labs registered on the platform.
Statistics recalculated weekly.

{"yearsCitations":{"type":"bar","data":{"show":true,"labels":[2021,2022,2023,2024],"ids":[0,0,0,0],"codes":[0,0,0,0],"imageUrls":["","","",""],"datasets":[{"label":"Citations number","data":[5,18,28,4],"backgroundColor":["#3B82F6","#3B82F6","#3B82F6","#3B82F6"],"percentage":["9.09","32.73","50.91","7.27"],"barThickness":null}]},"options":{"indexAxis":"x","maintainAspectRatio":true,"scales":{"y":{"ticks":{"precision":0,"autoSkip":false,"font":{"family":"Montserrat"},"color":"#000000"}},"x":{"ticks":{"stepSize":1,"precision":0,"font":{"family":"Montserrat"},"color":"#000000"}}},"plugins":{"legend":{"position":"top","labels":{"font":{"family":"Montserrat"},"color":"#000000"}},"title":{"display":true,"text":"Citations per year","font":{"size":24,"family":"Montserrat","weight":600},"color":"#000000"}}}},"journals":{"type":"bar","data":{"show":true,"labels":["International Journal of Molecular Sciences","Pharmaceutics","International Journal of Nanomedicine","Biomedicines","Frontiers in Cell and Developmental Biology","Food and Function","Open Research Europe","Plants","Nanomaterials","Membranes","Molecules","Applied Sciences (Switzerland)","Frontiers in Cardiovascular Medicine","Biocell","Cell Communication and Signaling","Fungal Biology and Biotechnology","Scientific Reports","Progress in Neurobiology","Expert Opinion on Therapeutic Patents","Journal of Nanobiotechnology","Fundamental Research","Seminars in Cancer Biology","Pharmacology and Therapeutics","Protein Expression and Purification","Pharmaceutical Development and Technology","Antioxidants","Nutrients","Journal of Phytopathology","ChemistryOpen"],"ids":[14627,4502,10956,24421,12128,13077,31128,17251,10051,6479,1770,16650,11659,5164,2290,17405,13767,7224,6211,11794,27258,19338,22929,2237,6847,16381,3372,14846,23757],"codes":[0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0,0],"imageUrls":["\/storage\/images\/resized\/MjH1ITP7lMYGxeqUZfkt2BnVLgjkk413jwBV97XX_medium.webp","\/storage\/images\/resized\/MjH1ITP7lMYGxeqUZfkt2BnVLgjkk413jwBV97XX_medium.webp","\/storage\/images\/resized\/wVWp6zaxUsMdR03dYMdOZoesUrVGtNMWkHKByIvT_medium.webp","\/storage\/images\/resized\/MjH1ITP7lMYGxeqUZfkt2BnVLgjkk413jwBV97XX_medium.webp","\/storage\/images\/resized\/4QWA67eqfcfyOiA8Wk7YnqroHFqQbTsmDJUYTCTg_medium.webp","\/storage\/images\/resized\/leiAYcRDGTSl5B1eCnwpSGqmDEUEfDPPoYisFGhT_medium.webp","\/storage\/images\/resized\/WEXVM2IukNfkmwoqmPhtMKmAeERljKWAbbXmEX7m_medium.webp","\/storage\/images\/resized\/MjH1ITP7lMYGxeqUZfkt2BnVLgjkk413jwBV97XX_medium.webp","\/storage\/images\/resized\/MjH1ITP7lMYGxeqUZfkt2BnVLgjkk413jwBV97XX_medium.webp","\/storage\/images\/resized\/MjH1ITP7lMYGxeqUZfkt2BnVLgjkk413jwBV97XX_medium.webp","\/storage\/images\/resized\/MjH1ITP7lMYGxeqUZfkt2BnVLgjkk413jwBV97XX_medium.webp","\/storage\/images\/resized\/MjH1ITP7lMYGxeqUZfkt2BnVLgjkk413jwBV97XX_medium.webp","\/storage\/images\/resized\/4QWA67eqfcfyOiA8Wk7YnqroHFqQbTsmDJUYTCTg_medium.webp","","\/storage\/images\/resized\/voXLqlsvTwv5p3iMQ8Dhs95nqB4AXOG7Taj7G4ra_medium.webp","\/storage\/images\/resized\/voXLqlsvTwv5p3iMQ8Dhs95nqB4AXOG7Taj7G4ra_medium.webp","\/storage\/images\/resized\/voXLqlsvTwv5p3iMQ8Dhs95nqB4AXOG7Taj7G4ra_medium.webp","\/storage\/images\/resized\/GDnYOu1UpMMfMMRV6Aqle4H0YLLsraeD9IP9qScG_medium.webp","\/storage\/images\/resized\/5YZtvLvkPZuc2JHOaZsjCvGSHFCuC3drUwN3YAc5_medium.webp","\/storage\/images\/resized\/voXLqlsvTwv5p3iMQ8Dhs95nqB4AXOG7Taj7G4ra_medium.webp","\/storage\/images\/resized\/GDnYOu1UpMMfMMRV6Aqle4H0YLLsraeD9IP9qScG_medium.webp","\/storage\/images\/resized\/GDnYOu1UpMMfMMRV6Aqle4H0YLLsraeD9IP9qScG_medium.webp","\/storage\/images\/resized\/GDnYOu1UpMMfMMRV6Aqle4H0YLLsraeD9IP9qScG_medium.webp","\/storage\/images\/resized\/GDnYOu1UpMMfMMRV6Aqle4H0YLLsraeD9IP9qScG_medium.webp","\/storage\/images\/resized\/5YZtvLvkPZuc2JHOaZsjCvGSHFCuC3drUwN3YAc5_medium.webp","\/storage\/images\/resized\/MjH1ITP7lMYGxeqUZfkt2BnVLgjkk413jwBV97XX_medium.webp","\/storage\/images\/resized\/MjH1ITP7lMYGxeqUZfkt2BnVLgjkk413jwBV97XX_medium.webp","\/storage\/images\/resized\/bRyGpdm98BkAUYiK1YFNpl5Z7hPu6Gd87gbIeuG3_medium.webp","\/storage\/images\/resized\/bRyGpdm98BkAUYiK1YFNpl5Z7hPu6Gd87gbIeuG3_medium.webp"],"datasets":[{"label":"","data":[5,3,3,2,2,2,1,1,1,1,1,1,1,1,1,1,1,1,1,1,1,1,1,1,1,1,1,1,1],"backgroundColor":["#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6"],"percentage":[9.09,5.45,5.45,3.64,3.64,3.64,1.82,1.82,1.82,1.82,1.82,1.82,1.82,1.82,1.82,1.82,1.82,1.82,1.82,1.82,1.82,1.82,1.82,1.82,1.82,1.82,1.82,1.82,1.82],"barThickness":13}]},"options":{"indexAxis":"y","maintainAspectRatio":false,"scales":{"y":{"ticks":{"precision":0,"autoSkip":false,"font":{"family":"Montserrat"},"color":"#000000"}},"x":{"ticks":{"stepSize":null,"precision":0,"font":{"family":"Montserrat"},"color":"#000000"}}},"plugins":{"legend":{"position":"top","labels":{"font":{"family":"Montserrat"},"color":"#000000"}},"title":{"display":true,"text":"Journals","font":{"size":24,"family":"Montserrat","weight":600},"color":"#000000"}}}},"publishers":{"type":"bar","data":{"show":true,"labels":["Multidisciplinary Digital Publishing Institute (MDPI)","Elsevier","Springer Nature","Frontiers Media S.A.","Royal Society of Chemistry (RSC)","Wiley","Dove Medical Press","Taylor & Francis","F1000 Research","Tech Science Press","American Society of Plant Biologists","Bentham Science"],"ids":[202,17,8,208,123,11,417,18,7910,8456,2122,39],"codes":[0,0,0,0,0,0,0,0,0,0,0,0],"imageUrls":["\/storage\/images\/resized\/MjH1ITP7lMYGxeqUZfkt2BnVLgjkk413jwBV97XX_medium.webp","\/storage\/images\/resized\/GDnYOu1UpMMfMMRV6Aqle4H0YLLsraeD9IP9qScG_medium.webp","\/storage\/images\/resized\/voXLqlsvTwv5p3iMQ8Dhs95nqB4AXOG7Taj7G4ra_medium.webp","\/storage\/images\/resized\/4QWA67eqfcfyOiA8Wk7YnqroHFqQbTsmDJUYTCTg_medium.webp","\/storage\/images\/resized\/leiAYcRDGTSl5B1eCnwpSGqmDEUEfDPPoYisFGhT_medium.webp","\/storage\/images\/resized\/bRyGpdm98BkAUYiK1YFNpl5Z7hPu6Gd87gbIeuG3_medium.webp","\/storage\/images\/resized\/wVWp6zaxUsMdR03dYMdOZoesUrVGtNMWkHKByIvT_medium.webp","\/storage\/images\/resized\/5YZtvLvkPZuc2JHOaZsjCvGSHFCuC3drUwN3YAc5_medium.webp","\/storage\/images\/resized\/WEXVM2IukNfkmwoqmPhtMKmAeERljKWAbbXmEX7m_medium.webp","","\/storage\/images\/resized\/JLpI53lI44aNyHLD8xZshTDqAobKeIZXi5qWe93H_medium.webp","\/storage\/images\/resized\/doUaFUZdxUEQjLi1TwZjGHi8HXYNWWSk04dSC6Xh_medium.webp"],"datasets":[{"label":"","data":[20,7,6,4,4,3,3,2,1,1,1,1],"backgroundColor":["#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6"],"percentage":[36.36,12.73,10.91,7.27,7.27,5.45,5.45,3.64,1.82,1.82,1.82,1.82],"barThickness":13}]},"options":{"indexAxis":"y","maintainAspectRatio":false,"scales":{"y":{"ticks":{"precision":0,"autoSkip":false,"font":{"family":"Montserrat"},"color":"#000000"}},"x":{"ticks":{"stepSize":null,"precision":0,"font":{"family":"Montserrat"},"color":"#000000"}}},"plugins":{"legend":{"position":"top","labels":{"font":{"family":"Montserrat"},"color":"#000000"}},"title":{"display":true,"text":"Publishers","font":{"size":24,"family":"Montserrat","weight":600},"color":"#000000"}}}}}

Publication PDF

Metrics

Cite this

GOST |

Cite this

GOST Copy

Garaeva L. et al. Delivery of functional exogenous proteins by plant-derived vesicles to human cells in vitro // Scientific Reports. 2021. Vol. 11. No. 1. 6489

GOST all authors (up to 50) Copy

Garaeva L., Kamyshinsky R., Kil Y., Varfolomeeva E., Verlov N., Komarova E., Garmay Y., Landa S., Burdakov V., Myasnikov A., Vinnikov I. A., Margulis B., Guzhova I., Kagansky A., Konevega A. L., Shtam T. Delivery of functional exogenous proteins by plant-derived vesicles to human cells in vitro // Scientific Reports. 2021. Vol. 11. No. 1. 6489

RIS |

Cite this

RIS Copy

TY - JOUR

DO - 10.1038/s41598-021-85833-y

UR - https://doi.org/10.1038%2Fs41598-021-85833-y

TI - Delivery of functional exogenous proteins by plant-derived vesicles to human cells in vitro

T2 - Scientific Reports

AU - Garaeva, Luiza

AU - Kamyshinsky, Roman

AU - Kil, Yury

AU - Varfolomeeva, Elena

AU - Verlov, Nikolai

AU - Komarova, Elena

AU - Garmay, Yuri

AU - Landa, Sergey

AU - Burdakov, Vladimir

AU - Myasnikov, Alexander

AU - Vinnikov, Ilya A.

AU - Margulis, Boris

AU - Guzhova, Irina

AU - Kagansky, Alexander

AU - Konevega, Andrey L.

AU - Shtam, Tatiana

PY - 2021

DA - 2021/03/22 00:00:00

PB - Springer Nature

IS - 1

VL - 11

SN - 2045-2322

ER -

BibTex

Cite this

BibTex Copy

@article{2021_Garaeva,

author = {Luiza Garaeva and Roman Kamyshinsky and Yury Kil and Elena Varfolomeeva and Nikolai Verlov and Elena Komarova and Yuri Garmay and Sergey Landa and Vladimir Burdakov and Alexander Myasnikov and Ilya A. Vinnikov and Boris Margulis and Irina Guzhova and Alexander Kagansky and Andrey L. Konevega and Tatiana Shtam},

title = {Delivery of functional exogenous proteins by plant-derived vesicles to human cells in vitro},

journal = {Scientific Reports},

year = {2021},

volume = {11},

publisher = {Springer Nature},

month = {mar},

url = {https://doi.org/10.1038%2Fs41598-021-85833-y},

number = {1},

doi = {10.1038/s41598-021-85833-y}

}

Found error?

Publisher

Springer Nature

Journal

Scientific Reports

Quartile SCImago

Quartile WOS

Impact factor

4.6

ISSN

20452322 (Print)

Labs

Resource Center