New insights of engineering plant exosome-like nanovesicles as a nanoplatform for therapeutics and drug delivery

Abstract

Plant exosome-like nanovesicles (PELNVs) are membrane-encapsulated nanostructures released from cells into their surroundings. PELNVs have an important role in intercellular and interspecies communication in all three domains of life. They act as protective compartments for the long-distance transit of signal molecules like proteins, nucleic acids, lipids, and other metabolites. A range of plants and vegetables can emit PELNVs. The importance of PELNVs in interspecies communication stems from their concentration in biomolecules (lipids, proteins, and miRNAs), lack of toxicity, ease of internalization by cells, and anti-inflammatory, immune-modulatory, and regenerative characteristics. PELNVs derived from numerous fruits and vegetables are biocompatible, biodegradable, and abundant in various plant species. Moreover, their convincing physicochemical characteristics underpin their modulative role in physiological and pathological processes, all of which have fueled speculation that these nanovesicles could be particularly adept at developing future-generation bio-therapeutic platforms. The goal of this review was not only to present an overview of the identified roles of PELNVs in physiology and pathology, but also to provide new insight toward their engineering for effective therapeutics and drug delivery nanoplatforms, a clue for future direction to the ongoing research gaps.

Keywords

Plant exosome-like nanovesicles (PELNVs) / engineering exosomes / nanotheranostics

References

[1] Fernandes M,Teixeira J,Gomes AC.Exosome-like nanoparticles: a new type of nanocarrier.Curr Med Chem2020;27:3888-905

[2] Cai Q,Wang M.Plants send small RNAs in extracellular vesicles to fungal pathogen to silence virulence genes.Science2018;360:1126-9 PMCID:PMC6442475

[3] Deng Z,Teng Y.Broccoli-derived nanoparticle inhibits mouse colitis by activating dendritic cell AMP-activated protein kinase.Mol Ther2017;25:1641-54 PMCID:PMC5498816

[4] Li Z,Yin H,Zhang HG.Arrowtail RNA for ligand display on ginger exosome-like nanovesicles to systemic deliver siRNA for cancer suppression.Sci Rep2018;8:14644 PMCID:PMC6168523

[5] Yang C,Merlin D.Advances in plant-derived edible nanoparticle-based lipid nano-drug delivery systems as therapeutic nanomedicines.J Mater Chem B2018;6:1312-21 PMCID:PMC6053076

[6] Wang Q,Mu J.Grapefruit-derived nanovectors use an activated leukocyte trafficking pathway to deliver therapeutic agents to inflammatory tumor sites.Cancer Res2015;75:2520-9 PMCID:PMC4470740

[7] Zieske JD,Guo X.Extracellular vesicles and cell-cell communication in the cornea.Anat Rec (Hoboken)2020;303:1727-34 PMCID:PMC6881515

[8] Gioia S, Hossain MN, Conese M. Biological properties and therapeutic effects of plant-derived nanovesicles.Open Med (Wars)2020;15:1096-122 PMCID:PMC7718644

[9] Teng Y,Sayed M.Plant-derived exosomal microRNAs shape the gut microbiota.Cell Host Microbe2018;24:637-652.e8 PMCID:PMC6746408

[10] You JY,Rhee WJ.Isolation of cabbage exosome-like nanovesicles and investigation of their biological activities in human cells.Bioact Mater2021;6:4321-32 PMCID:PMC8105599

[11] Kučuk N,Knez Ž.Exosomes engineering and their roles as therapy delivery tools, therapeutic targets, and biomarkers.Int J Mol Sci2021;22:9543 PMCID:PMC8431173

[12] Gurung S,Touramanidou L.The exosome journey: from biogenesis to uptake and intracellular signalling.Cell Commun Signal2021;19:47 PMCID:PMC8063428

[13] Regente M,San Clemente H,Jamet E.Plant extracellular vesicles are incorporated by a fungal pathogen and inhibit its growth.J Exp Bot2017;68:5485-95

[14] Jafari D,Jafari R.Designer exosomes: a new platform for biotechnology therapeutics.BioDrugs2020;34:567-86 PMCID:PMC7402079

[15] Ohno S,Sudo K.Systemically injected exosomes targeted to EGFR deliver antitumor microRNA to breast cancer cells.Mol Ther2013;21:185-91 PMCID:PMC3538304

[16] Chen H,Zeng X.Exosomes, a new star for targeted delivery.Front Cell Dev Biol2021;9:751079 PMCID:PMC8531489

[17] Kooijmans SA,Roffler SR,Vader P.Display of GPI-anchored anti-EGFR nanobodies on extracellular vesicles promotes tumour cell targeting.J Extracell Vesicles2016;5:31053 PMCID:PMC4793259

[18] Gilligan KE.Engineering exosomes for cancer therapy.Int J Mol Sci2017;18:1122 PMCID:PMC5485946

[19] Liang Y,Lu J.Engineering exosomes for targeted drug delivery.Theranostics2021;11:3183-95 PMCID:PMC7847680

[20] Alvarez-Erviti L,Yin H,Lakhal S.Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes.Nat Biotechnol2011;29:341-5

[21] Liang Y,Li X.Chondrocyte-targeted microRNA delivery by engineered exosomes toward a cell-free osteoarthritis therapy.ACS Appl Mater Interfaces2020;12:36938-47

[22] Xu X,Li X.Exosome-mediated delivery of kartogenin for chondrogenesis of synovial fluid-derived mesenchymal stem cells and cartilage regeneration.Biomaterials2021;269:120539

[23] Vogt S,Grillari J,Wozniak-knopp G.Engineering of surface proteins in extracellular vesicles for tissue-specific targeting. In: Shiomi N, editor. Current topics in biochemical engineering. IntechOpen; 2019.

[24] Richter M,Fuhrmann G.Approaches to surface engineering of extracellular vesicles.Adv Drug Deliv Rev2021;173:416-26

[25] Richardson JJ.Surface engineering of extracellular vesicles through chemical and biological strategies.Chem Mater2019;31:2191-201

[26] Cheng Q,Han M,Lenz HJ.Reprogramming exosomes as nanoscale controllers of cellular immunity.J Am Chem Soc2018;140:16413-7 PMCID:PMC6469991

[27] Dad HA,Zhu AQ,Peng LH.Plant exosome-like nanovesicles: emerging therapeutics and drug delivery nanoplatforms.Mol Ther2021;29:13-31 PMCID:PMC7791080

[28] Li P,Lee SH,Gao Z.Progress in exosome isolation techniques.Theranostics2017;7:789-804 PMCID:PMC5327650

[29] Loureiro JA,Duarte A.Resveratrol and grape extract-loaded solid lipid nanoparticles for the treatment of alzheimer’s disease.Molecules2017;22:277

[30] García-Manrique P,Gutiérrez G,Blanco-López MC.Therapeutic biomaterials based on extracellular vesicles: classification of bio-engineering and mimetic preparation routes.J Extracell Vesicles2018;7:1422676 PMCID:PMC5774402

[31] Antimisiaris SG,Marazioti A.Exosomes and exosome-inspired vesicles for targeted drug delivery.Pharmaceutics2018;10:218 PMCID:PMC6321407

[32] Li YJ,Liu J.Artificial exosomes for translational nanomedicine.J Nanobiotechnology2021;19:242 PMCID:PMC8359033

[33] Villarroya-Beltri C,Gutiérrez-Vázquez C,Mittelbrunn M.Sorting it out: regulation of exosome loading.Semin Cancer Biol2014;28:3-13 PMCID:PMC4640178

[34] Prado N,Villalba M,Batanero E.Bystander suppression to unrelated allergen sensitization through intranasal administration of tolerogenic exosomes in mouse.Mol Immunol2010;47:2148-51

[35] Jeppesen DK,Primdahl-Bengtson B.Comparative analysis of discrete exosome fractions obtained by differential centrifugation.J Extracell Vesicles2014;3:25011 PMCID:PMC4224706

[36] Kalra H,Liem M.Comparative proteomics evaluation of plasma exosome isolation techniques and assessment of the stability of exosomes in normal human blood plasma.Proteomics2013;13:3354-64

[37] Fujita D,Komori H.Apple-derived nanoparticles modulate expression of organic-anion-transporting polypeptide (OATP) 2B1 in Caco-2 cells.Mol Pharm2018;15:5772-80

[38] Duan L,Xu X.Exosome-mediated delivery of gene vectors for gene therapy.Nanoscale2021;13:1387-97

[39] Han Y,Dutta S.Overview and update on methods for cargo loading into extracellular vesicles.Processes (Basel)2021;9:356 PMCID:PMC8096148

[40] György B,Breakefield XO.Therapeutic applications of extracellular vesicles: clinical promise and open questions.Annu Rev Pharmacol Toxicol2015;55:439-64 PMCID:PMC4445965

[41] Fan Y.Development of liposomal formulations: from concept to clinical investigations.Asian J Pharm2013;8:81-7

[42] Theek B,Ojha T.Sonoporation enhances liposome accumulation and penetration in tumors with low EPR.J Control Release2016;231:77-85 PMCID:PMC5404719

[43] Zhang M,Prasad M.Edible ginger-derived nanoparticles: a novel therapeutic approach for the prevention and treatment of inflammatory bowel disease and colitis-associated cancer.Biomaterials2016;101:321-40 PMCID:PMC4921206

[44] Zhang M,Xu C.Plant derived edible nanoparticles as a new therapeutic approach against diseases.Tissue Barriers2016;4:e1134415 PMCID:PMC4910829

[45] Sung J,Collins JF.Preparation and characterization of ginger lipid-derived nanoparticles for colon-targeted siRNA delivery.Bio Protoc2020;10:e3685 PMCID:PMC7416531

[46] Zhang M,Han MK,Merlin D.Oral administration of ginger-derived nanolipids loaded with siRNA as a novel approach for efficient siRNA drug delivery to treat ulcerative colitis.Nanomedicine (Lond)2017;12:1927-43 PMCID:PMC5827822

[47] Woith E,Hausman JF.Plant extracellular vesicles and nanovesicles: focus on secondary metabolites, proteins and lipids with perspectives on their potential and sources.Int J Mol Sci2021;22:3719 PMCID:PMC8038311

[48] Yu L,Liu L,Wang C.Plant-derived nanovesicles: a novel form of nanomedicine.Front Bioeng Biotechnol2020;8:584391 PMCID:PMC7591720

[49] Jan AT,Badierah R.Expedition into exosome biology: a perspective of progress from discovery to therapeutic development.Cancers (Basel)2021;13:1157 PMCID:PMC7962655

[50] Johnsen KB,Skov MN,Moos T.A comprehensive overview of exosomes as drug delivery vehicles - endogenous nanocarriers for targeted cancer therapy.Biochim Biophys Acta2014;1846:75-87

[51] Zhu L,Yuhan J.Exosomes mediated the delivery of ochratoxin A-induced cytotoxicity in HEK293 cells.Toxicology2021;461:152926

[52] Harishkumar M,Yuichi N.Designer exosomes: smart nano-communication tools for translational medicine.Bioengineering (Basel)2021;8:158 PMCID:PMC8615258

[53] Garaeva L,Kil Y.Delivery of functional exogenous proteins by plant-derived vesicles to human cells in vitro.Sci Rep2021;11:6489 PMCID:PMC7985202

[54] Nunes SS,Cavalcante CH.Influence of PEG coating on the biodistribution and tumor accumulation of pH-sensitive liposomes.Drug Deliv Transl Res2019;9:123-30 PMCID:PMC6361166

[55] Ito Y,Kuranaga Y.Uptake of microRNAs from exosome-like nanovesicles of edible plant juice by rat enterocytes.Int J Mol Sci2021;22:3749 PMCID:PMC8038500

[56] Wang MZ,Ma HJ.Transdermal siRNA delivery by pH-switchable micelles with targeting effect suppress skin melanoma progression.J Control Release2020;322:95-107

[57] Yang C,Lama S,Merlin D.Natural-lipid nanoparticle-based therapeutic approach to deliver 6-shogaol and its metabolites M2 and M13 to the colon to treat ulcerative colitis.J Control Release2020;323:293-310 PMCID:PMC7299768

[58] Gao C,Zhou Y,Wang S.Novel drug delivery systems of Chinese medicine for the treatment of inflammatory bowel disease.Chin Med2019;14:23 PMCID:PMC6580650

[59] Raimondo S,Fontana S.Citrus limon-derived nanovesicles inhibit cancer cell proliferation and suppress CML xenograft growth by inducing TRAIL-mediated cell death.Oncotarget2015;6:19514-27 PMCID:PMC4637302

[60] Ju S,Dokland T.Grape exosome-like nanoparticles induce intestinal stem cells and protect mice from DSS-induced colitis.Mol Ther2013;21:1345-57 PMCID:PMC3702113

[61] Kim H,Cho H.Recent advances in exosome-based drug delivery for cancer therapy.Cancers (Basel)2021;13:4435 PMCID:PMC8430743

[62] Sarvarian P,Gholipour E.Application of emerging plant-derived nanoparticles as a novel approach for nano-drug delivery systems.Immunol Invest2022;51:1039-59