Biodistribution of therapeutic extracellular vesicles

Dhanu Gupta , Oscar P.B Wiklander , Matthew J.A Wood , Samir El-Andaloussi

Extracellular Vesicles and Circulating Nucleic Acids ›› 2023, Vol. 4 ›› Issue (2) : 170 -90.

PDF
Extracellular Vesicles and Circulating Nucleic Acids ›› 2023, Vol. 4 ›› Issue (2) :170 -90. DOI: 10.20517/evcna.2023.12
Review

Biodistribution of therapeutic extracellular vesicles

Author information +
History +
PDF

Abstract

The field of extracellular vesicles (EVs) has seen a tremendous paradigm shift in the past two decades, from being regarded as cellular waste bags to being considered essential mediators in intercellular communication. Their unique ability to transfer macromolecules across cells and biological barriers has made them a rising star in drug delivery. Mounting evidence suggests that EVs can be explored as efficient drug delivery vehicles for a range of therapeutic macromolecules. In contrast to many synthetic delivery systems, these vesicles appear exceptionally well tolerated in vivo. This tremendous development in the therapeutic application of EVs has been made through technological advancement in labelling and understanding the in vivo biodistribution of EVs. Here in this review, we have summarised the recent findings in EV in vivo pharmacokinetics and discussed various biological barriers that need to be surpassed to achieve tissue-specific delivery.

Keywords

Exosomes / in vivo biodistribution / extracellular vesicles / targeted delivery / CNS targeting

Cite this article

Download citation ▾
Dhanu Gupta, Oscar P.B Wiklander, Matthew J.A Wood, Samir El-Andaloussi. Biodistribution of therapeutic extracellular vesicles. Extracellular Vesicles and Circulating Nucleic Acids, 2023, 4(2): 170-90 DOI:10.20517/evcna.2023.12

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

Teng F.Shedding light on extracellular vesicle biogenesis and bioengineering.Adv Sci (Weinh)2020;8:2003505 PMCID:PMC7788585

[2]

van Niel G,Raposo G.Shedding light on the cell biology of extracellular vesicles.Nat Rev Mol Cell Biol2018;19:213-28

[3]

Willms E,Mäger I,Vader P.Extracellular vesicle heterogeneity: subpopulations, isolation techniques, and diverse functions in cancer progression.Front Immunol2018;9:738 PMCID:PMC5936763

[4]

Pegtel DM.Exosomes.Annu Rev Biochem2019;88:487-514

[5]

Wiklander OPB,Lötvall J,El Andaloussi S.Advances in therapeutic applications of extracellular vesicles.Sci Transl Med2019;11 PMCID:PMC7104415

[6]

Gupta D,Görgens A.Amelioration of systemic inflammation via the display of two different decoy protein receptors on extracellular vesicles.Nat Biomed Eng2021;5:1084-98

[7]

Verweij FJ,Boulanger CM.The power of imaging to understand extracellular vesicle biology in vivo.Nat Methods2021;18:1013-26 PMCID:PMC8796660

[8]

Ramirez MI,Gadelha C.Technical challenges of working with extracellular vesicles.Nanoscale2018;10:881-906

[9]

Lee YXF,Wood MJA.Considerations and implications in the purification of extracellular vesicles - a cautionary tale.Front Neurosci2019;13:1067 PMCID:PMC6813730

[10]

Liangsupree T,Riekkola ML.Modern isolation and separation techniques for extracellular vesicles.J Chromatogr A2021;1636:461773

[11]

Sork H,Corso G.Profiling of extracellular small RNAs highlights a strong bias towards non-vesicular secretion.Cells2021;10:1543

[12]

Whittaker TE,Nele V,Stevens MM.Experimental artefacts can lead to misattribution of bioactivity from soluble mesenchymal stem cell paracrine factors to extracellular vesicles.J Extracell Vesicles2020;9:1807674 PMCID:PMC7480412

[13]

Brennan K,FitzGerald SP.A comparison of methods for the isolation and separation of extracellular vesicles from protein and lipid particles in human serum.Sci Rep2020;10:1039 PMCID:PMC6978318

[14]

Meng W,Hao Y,Li L.Prospects and challenges of extracellular vesicle-based drug delivery system: considering cell source.Drug Deliv2020;27:585-98 PMCID:PMC7178886

[15]

Bellotti C,Kuplennik N,Steinfeld R.High-grade extracellular vesicles preparation by combined size-exclusion and affinity chromatography.Sci Rep2021;11:10550 PMCID:PMC8131383

[16]

Simonsen JB.What are we looking at?.Circ Res2017;121:920-2

[17]

Sódar BW,Pálóczi K.Low-density lipoprotein mimics blood plasma-derived exosomes and microvesicles during isolation and detection.Sci Rep2016;6:24316

[18]

McNamara RP.Modern techniques for the isolation of extracellular vesicles and viruses.J Neuroimmune Pharmacol2020;15:459-72 PMCID:PMC7065924

[19]

Van Deun J,Agostinis P.EV-TRACK ConsortiumEV-TRACK: transparent reporting and centralizing knowledge in extracellular vesicle research.Nat Methods2017;14:228-32

[20]

Théry C,Raposo G.Isolation and characterization of exosomes from cell culture supernatants and biological fluids.Curr Protoc Cell Biol2006;Chapter 3:Unit 3.22

[21]

Zhang Q,Jeppesen DK.Transfer of functional cargo in exomeres.Cell Rep2019;27:940-954.e6 PMCID:PMC6559347

[22]

Webber J.How pure are your vesicles?.J Extracell Vesicles2013;2:19861 PMCID:PMC3760653

[23]

Tauro BJ,Mathias RA.Comparison of ultracentrifugation, density gradient separation, and immunoaffinity capture methods for isolating human colon cancer cell line LIM1863-derived exosomes.Methods2012;56:293-304

[24]

Iwai K,Suga K,Shiba K.Isolation of human salivary extracellular vesicles by iodixanol density gradient ultracentrifugation and their characterizations.J Extracell Vesicles2016;5:30829 PMCID:PMC4871899

[25]

Mol EA,Doevendans PA,Vader P.Higher functionality of extracellular vesicles isolated using size-exclusion chromatography compared to ultracentrifugation.Nanomedicine2017;13:2061-5

[26]

Nordin JZ,Vader P.Ultrafiltration with size-exclusion liquid chromatography for high yield isolation of extracellular vesicles preserving intact biophysical and functional properties.Nanomedicine2015;11:879-83

[27]

Desai MA,Burns M.Application of chromatography in the downstream processing of biomolecules. In: Desai MA, editor. Downstream processing of proteins. Totowa: Humana Press; 2000. p. 73-94.

[28]

Monguió-Tortajada M,Bayes-Genis A,Borràs FE.Extracellular vesicle isolation methods: rising impact of size-exclusion chromatography.Cell Mol Life Sci2019;76:2369-82

[29]

Whitford W.Exosome manufacturing status.Future Med Chem2019;11:1225-36

[30]

Lee JH,Go HK.Reproducible large-scale isolation of exosomes from adipose tissue-derived mesenchymal stem/stromal cells and their application in acute kidney injury.Int J Mol Sci2020;21:4774 PMCID:PMC7370182

[31]

Busatto S,Ticer T.Tangential flow filtration for highly efficient concentration of extracellular vesicles from large volumes of fluid.Cells2018;7:273 PMCID:PMC6315734

[32]

Corso G,Lee Y.Reproducible and scalable purification of extracellular vesicles using combined bind-elute and size exclusion chromatography.Sci Rep2017;7:11561 PMCID:PMC5599601

[33]

Lobb RJ,Wen SW.Optimized exosome isolation protocol for cell culture supernatant and human plasma.J Extracell Vesicles2015;4:27031 PMCID:PMC4507751

[34]

Mendt M,Sugimoto H.Generation and testing of clinical-grade exosomes for pancreatic cancer.JCI Insight2018;3:99263 PMCID:PMC5931131

[35]

Willis GR,Mitsialis SA.Toward exosome-based therapeutics: isolation, heterogeneity, and fit-for-purpose potency.Front Cardiovasc Med2017;4:63 PMCID:PMC5640880

[36]

Staubach S,Tertel T.Scaled preparation of extracellular vesicles from conditioned media.Adv Drug Deliv Rev2021;177:113940

[37]

Oksvold MP,Pedersen KW.Magnetic bead-based isolation of exosomes. In: Sioud M, editor. RNA interference. New York: Springer; 2015. p. 465-81.

[38]

Clayton A,Navabi H.Analysis of antigen presenting cell derived exosomes, based on immuno-magnetic isolation and flow cytometry.J Immunol Methods2001;247:163-74

[39]

Ghosh A,Chute IC.Rapid isolation of extracellular vesicles from cell culture and biological fluids using a synthetic peptide with specific affinity for heat shock proteins.PLoS One2014;9:e110443 PMCID:PMC4201556

[40]

Grant R,Stratton D.A filtration-based protocol to isolate human plasma membrane-derived vesicles and exosomes from blood plasma.J Immunol Methods2011;371:143-51

[41]

Balaj L,Chen W.Heparin affinity purification of extracellular vesicles.Sci Rep2015;5:10266 PMCID:PMC4437317

[42]

Royo F,Sanchez-Mosquera P.Different EV enrichment methods suitable for clinical settings yield different subpopulations of urinary extracellular vesicles from human samples.J Extracell Vesicles2016;5:29497 PMCID:PMC4759834

[43]

Royo F,Tackett MR.Comparative miRNA analysis of urine extracellular vesicles isolated through five different methods.Cancers (Basel)2016;8:112 PMCID:PMC5187510

[44]

Samsonov R,Burdakov V.Lectin-induced agglutination method of urinary exosomes isolation followed by mi-RNA analysis: application for prostate cancer diagnostic.Prostate2016;76:68-79

[45]

Gallart-Palau X,Wong AS.Extracellular vesicles are rapidly purified from human plasma by PRotein Organic Solvent PRecipitation (PROSPR).Sci Rep2015;5:14664 PMCID:PMC4588595

[46]

Deregibus MC,D'Antico S.Charge-based precipitation of extracellular vesicles.Int J Mol Med2016;38:1359-66 PMCID:PMC5065305

[47]

Guzman NA.A two-dimensional affinity capture and separation mini-platform for the isolation, enrichment, and quantification of biomarkers and its potential use for liquid biopsy.Biomedicines2020;8:255 PMCID:PMC7459796

[48]

Whiteside TL.Extracellular vesicles isolation and their biomarker potential: are we ready for testing?.Ann Transl Med2017;5:54 PMCID:PMC5326637

[49]

Jauregui R,Vojtech LN.Temperature-responsive magnetic nanoparticles for enabling affinity separation of extracellular vesicles.ACS Appl Mater Interfaces2018;10:33847-56 PMCID:PMC6538933

[50]

Zhang K,Wu S,Shi J.Rapid capture and nondestructive release of extracellular vesicles using aptamer-based magnetic isolation.ACS Sens2019;4:1245-51

[51]

Chen J,Lu Y.Isolation and visible detection of tumor-derived exosomes from plasma.Anal Chem2018;90:14207-15

[52]

Kim DK,An SY,Bartosh TJ.Chromatographically isolated CD63+CD81+ extracellular vesicles from mesenchymal stromal cells rescue cognitive impairments after TBI.Proc Natl Acad Sci USA2016;113:170-5 PMCID:PMC4711859

[53]

Agarwal K,Lazaroff SM,Ringel MD.Analysis of exosome release as a cellular response to MAPK pathway inhibition.Langmuir2015;31:5440-8 PMCID:PMC4589192

[54]

Zhang H,Kim HS.Identification of distinct nanoparticles and subsets of extracellular vesicles by asymmetric flow field-flow fractionation.Nat Cell Biol2018;20:332-43 PMCID:PMC5931706

[55]

Maeki M,Sato Y,Tokeshi M.Advances in microfluidics for lipid nanoparticles and extracellular vesicles and applications in drug delivery systems.Adv Drug Deliv Rev2018;128:84-100

[56]

Liang LG,Zhou S.An integrated double-filtration microfluidic device for isolation, enrichment and quantification of urinary extracellular vesicles for detection of bladder cancer.Sci Rep2017;7:46224 PMCID:PMC5402302

[57]

Hartjes TA,Jenster GW,van Royen ME.Extracellular vesicle quantification and characterization: common methods and emerging approaches.Bioengineering (Basel)2019;6:7 PMCID:PMC6466085

[58]

Sokolova V,Hornung S.Characterisation of exosomes derived from human cells by nanoparticle tracking analysis and scanning electron microscopy.Colloids Surf B Biointerfaces2011;87:146-50

[59]

de Vrij J,van-Nispen M.Quantification of nanosized extracellular membrane vesicles with scanning ion occlusion sensing.Nanomedicine (Lond)2013;8:1443-58

[60]

Andreu Z,Sanguino-Pascual A.Comparative analysis of EV isolation procedures for miRNAs detection in serum samples.J Extracell Vesicles2016;5:31655 PMCID:PMC4916259

[61]

Nath Neerukonda S,Patria J.Comparison of exosomes purified via ultracentrifugation (UC) and Total Exosome Isolation (TEI) reagent from the serum of Marek's disease virus (MDV)-vaccinated and tumor-bearing chickens.J Virol Methods2019;263:1-9

[62]

van der Vlist EJ,Stoorvogel W,Wauben MH.Fluorescent labeling of nano-sized vesicles released by cells and subsequent quantitative and qualitative analysis by high-resolution flow cytometry.Nat Protoc2012;7:1311-26

[63]

Nolte-'t Hoen EN,Aalberts M.Quantitative and qualitative flow cytometric analysis of nanosized cell-derived membrane vesicles.Nanomedicine2012;8:712-20 PMCID:PMC7106164

[64]

Ricklefs FL,Reimer R.Imaging flow cytometry facilitates multiparametric characterization of extracellular vesicles in malignant brain tumours.J Extracell Vesicles2019;8:1588555 PMCID:PMC6442086

[65]

Görgens A,Ferrer-Tur R.Optimisation of imaging flow cytometry for the analysis of single extracellular vesicles by using fluorescence-tagged vesicles as biological reference material.J Extracell Vesicles2019;8:1587567 PMCID:PMC6442110

[66]

Nolan JP.Analysis of individual extracellular vesicles by flow cytometry. In: Hawley TS, Hawley RG, editors. Flow cytometry protocols. New York: Springer; 2018. p. 79-92.

[67]

Rikkert LG,Terstappen LWMM.Quality of extracellular vesicle images by transmission electron microscopy is operator and protocol dependent.J Extracell Vesicles2019;8:1555419 PMCID:PMC6327933

[68]

Théry C,Aikawa E.Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines.J Extracell Vesicles2018;7:1535750 PMCID:PMC6322352

[69]

Wiklander OPB,Welsh JA.Systematic methodological evaluation of a multiplex bead-based flow cytometry assay for detection of extracellular vesicle surface signatures.Front Immunol2018;9:1326 PMCID:PMC6008374

[70]

Duijvesz D,van der Fels CA.Immuno-based detection of extracellular vesicles in urine as diagnostic marker for prostate cancer.Int J Cancer2015;137:2869-78

[71]

Koliha N,Heider U.A novel multiplex bead-based platform highlights the diversity of extracellular vesicles.J Extracell Vesicles2016;5:29975 PMCID:PMC4762227

[72]

Xia Y,Wang L.A visible and colorimetric aptasensor based on DNA-capped single-walled carbon nanotubes for detection of exosomes.Biosens Bioelectron2017;92:8-15

[73]

Lai RC,Yeo RW.MSC secretes at least 3 EV types each with a unique permutation of membrane lipid, protein and RNA.J Extracell Vesicles2016;5:29828 PMCID:PMC4770866

[74]

Liang K,Fan J.Nanoplasmonic quantification of tumor-derived extracellular vesicles in plasma microsamples for diagnosis and treatment monitoring.Nat Biomed Eng2017;1:0021 PMCID:PMC5543996

[75]

Gupta D,El Andaloussi S.Dosing extracellular vesicles.Adv Drug Deliv Rev2021;178:113961

[76]

Wiklander OP,O'Loughlin A.Extracellular vesicle in vivo biodistribution is determined by cell source, route of administration and targeting.J Extracell Vesicles2015;4:26316 PMCID:PMC4405624

[77]

Pužar Dominkuš P,Sitar S.PKH26 labeling of extracellular vesicles: Characterization and cellular internalization of contaminating PKH26 nanoparticles.Biochim Biophys Acta Biomembr2018;1860:1350-61

[78]

Simonsen JB.Pitfalls associated with lipophilic fluorophore staining of extracellular vesicles for uptake studies.J Extracell Vesicles2019;8:1582237 PMCID:PMC6383605

[79]

Dehghani M,Flax J.Systematic evaluation of PKH labelling on extracellular vesicle size by nanoparticle tracking analysis.Sci Rep2020;10:9533 PMCID:PMC7293335

[80]

Gupta D,Pavlova S.Quantification of extracellular vesicles in vitro and in vivo using sensitive bioluminescence imaging.J Extracell Vesicles2020;9:1800222 PMCID:PMC7481830

[81]

Kooijmans SAA,Schiffelers RM.Recombinant phosphatidylserine-binding nanobodies for targeting of extracellular vesicles to tumor cells: a plug-and-play approach.Nanoscale2018;10:2413-26 PMCID:PMC5795695

[82]

Lai CP,Ericsson M.Dynamic biodistribution of extracellular vesicles in vivo using a multimodal imaging reporter.ACS Nano2014;8:483-94 PMCID:PMC3934350

[83]

Teare GF,Slezak SE,Hay JB.Long-term tracking of lymphocytes in vivo: the migration of PKH-labeled lymphocytes.Cell Immunol1991;134:157-70

[84]

Cilliers C,Atangcho L.Residualization rates of near-infrared dyes for the rational design of molecular imaging agents.Mol Imaging Biol2015;17:757-62 PMCID:PMC4938006

[85]

Varga Z,Pálóczi K.Radiolabeling of extracellular vesicles with 99mTc for quantitative in vivo imaging studies.Cancer Biother Radiopharm2016;31:168-73

[86]

Morishita M,Nishikawa M.Quantitative analysis of tissue distribution of the B16BL6-derived exosomes using a streptavidin-lactadherin fusion protein and iodine-125-labeled biotin derivative after intravenous injection in mice.J Pharm Sci2015;104:705-13

[87]

Smyth T,Malik N,Graner MW.Biodistribution and delivery efficiency of unmodified tumor-derived exosomes.J Control Release2015;199:145-55 PMCID:PMC4441346

[88]

Hu L,Hood JL.Magnetic resonance imaging of melanoma exosomes in lymph nodes.Magn Reson Med2015;74:266-71 PMCID:PMC4422779

[89]

Busato A,Bontempi P.Magnetic resonance imaging of ultrasmall superparamagnetic iron oxide-labeled exosomes from stem cells: a new method to obtain labeled exosomes.Int J Nanomedicine2016;11:2481-90 PMCID:PMC4898039

[90]

Luo W,Chen Z,Andrade-Powell KC.Spatial and temporal tracking of cardiac exosomes in mouse using a nano-luciferase-CD63 fusion protein.Commun Biol2020;3:114 PMCID:PMC7064570

[91]

Corso G,Trojer D.Systematic characterization of extracellular vesicle sorting domains and quantification at the single molecule - single vesicle level by fluorescence correlation spectroscopy and single particle imaging.J Extracell Vesicles2019;8:1663043 PMCID:PMC6758720

[92]

Silva AM,Gunnarsson A.Quantification of protein cargo loading into engineered extracellular vesicles at single-vesicle and single-molecule resolution.J Extracell Vesicles2021;10:e12130 PMCID:PMC8329990

[93]

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

[94]

Rashid MH,Ara R.Differential in vivo biodistribution of 131I-labeled exosomes from diverse cellular origins and its implication for theranostic application.Nanomedicine2019;21:102072

[95]

Lázaro-Ibáñez E,Saleh AF.Selection of fluorescent, bioluminescent, and radioactive tracers to accurately reflect extracellular vesicle biodistribution in vivo.ACS Nano2021;15:3212-27

[96]

Kang M,Blenkiron C.Biodistribution of extracellular vesicles following administration into animals: a systematic review.J Extracell Vesicles2021;10:e12085 PMCID:PMC8224174

[97]

Takov K,Davidson SM.Confounding factors in vesicle uptake studies using fluorescent lipophilic membrane dyes.J Extracell Vesicles2017;6:1388731 PMCID:PMC5699187

[98]

Dehghani M,Flax J.Exosome labeling by lipophilic dye PKH26 results in significant increase in vesicle size.BioRxiv2019;preprint

[99]

Skotland T,Llorente A.Biodistribution, pharmacokinetics and excretion studies of intravenously injected nanoparticles and extracellular vesicles: Possibilities and challenges.Adv Drug Deliv Rev2022;186:114326

[100]

Faruqu FN,Xu L.Membrane Radiolabelling of exosomes for comparative biodistribution analysis in immunocompetent and immunodeficient mice - a novel and universal approach.Theranostics2019;9:1666-82 PMCID:PMC6485196

[101]

Choi H,Mirzaaghasi A.Exosome-based delivery of super-repressor IκBα relieves sepsis-associated organ damage and mortality.Sci Adv2020;6:eaaz6980 PMCID:PMC7141819

[102]

Imai T,Nishikawa M.Macrophage-dependent clearance of systemically administered B16BL6-derived exosomes from the blood circulation in mice.J Extracell Vesicles2015;4:26238 PMCID:PMC4323410

[103]

Skotland T.Transport of nanoparticles across the endothelial cell layer.Nano Today2021;36:101029

[104]

Barua S.Challenges associated with penetration of nanoparticles across cell and tissue barriers: a review of current status and future prospects.Nano Today2014;9:223-43 PMCID:PMC4129396

[105]

Aird WC.Phenotypic heterogeneity of the endothelium: I. Structure, function, and mechanisms.Circ Res2007;100:158-73

[106]

Sarin H.Physiologic upper limits of pore size of different blood capillary types and another perspective on the dual pore theory of microvascular permeability.J Angiogenes Res2010;2:14 PMCID:PMC2928191

[107]

Hennigs JK,Trepel M.Vascular endothelial cells: heterogeneity and targeting approaches.Cells2021;10:2712 PMCID:PMC8534745

[108]

Szafranska K,Holte CF,Zapotoczny B.The wHole story about fenestrations in LSEC.Front Physiol2021;12:1468 PMCID:PMC8473804

[109]

Kadry H,Cucullo L.A blood-brain barrier overview on structure, function, impairment, and biomarkers of integrity.Fluids Barriers CNS2020;17:69 PMCID:PMC7672931

[110]

Claesson-Welsh L,McDonald DM.Permeability of the endothelial barrier: identifying and reconciling controversies.Trends Mol Med2021;27:314-31 PMCID:PMC8005435

[111]

Khan AI,Du D,Dutta P.Quantification of kinetic rate constants for transcytosis of polymeric nanoparticle through blood-brain barrier.Biochim Biophys Acta Gen Subj2018;1862:2779-87 PMCID:PMC6195830

[112]

Morad G,Hagedorn EJ.Tumor-derived extracellular vesicles breach the intact blood-brain barrier via transcytosis.ACS Nano2019;13:13853-65 PMCID:PMC7169949

[113]

Ghersi-Egea JF,Catala M,Doetsch F.Molecular anatomy and functions of the choroidal blood-cerebrospinal fluid barrier in health and disease.Acta Neuropathol2018;135:337-61

[114]

Grapp M,Schweizer M.Choroid plexus transcytosis and exosome shuttling deliver folate into brain parenchyma.Nat Commun2013;4:2123

[115]

Hobbs SK,Yuan F.Regulation of transport pathways in tumor vessels: role of tumor type and microenvironment.Proc Natl Acad Sci USA1998;95:4607-12 PMCID:PMC22537

[116]

Moulton KS,Sonn S,Zurakowski D.Loss of collagen XVIII enhances neovascularization and vascular permeability in atherosclerosis.Circulation2004;110:1330-6

[117]

Nehoff H,Domanovitch L,Greish K.Nanomedicine for drug targeting: strategies beyond the enhanced permeability and retention effect.Int J Nanomedicine2014;9:2539-55 PMCID:PMC4039421

[118]

Yuan D,Banks WA.Macrophage exosomes as natural nanocarriers for protein delivery to inflamed brain.Biomaterials2017;142:1-12 PMCID:PMC5603188

[119]

Mirzaaghasi A,Ahn SH,Park JH.Biodistribution and pharmacokinectics of liposomes and exosomes in a mouse model of sepsis.Pharmaceutics2021;13:427 PMCID:PMC8004782

[120]

Banks WA,Hansen KM,Whiteside TL.Characteristics of exosomes and the vascular landscape regulate exosome sequestration by peripheral tissues and brain.Int J Mol Sci2022;23:12513 PMCID:PMC9603979

[121]

Gordon S.The mononuclear phagocytic system. Generation of diversity.Front Immunol2019;10:1893 PMCID:PMC6696592

[122]

Tsoi KM,Ma XZ.Mechanism of hard-nanomaterial clearance by the liver.Nat Mater2016;15:1212-21 PMCID:PMC5132626

[123]

Ishibashi H,Komori A,Shimoda S.Liver architecture, cell function, and disease.Semin Immunopathol2009;31:399-409

[124]

MacPhee PJ,Groom AC.Intermittence of blood flow in liver sinusoids, studied by high-resolution in vivo microscopy.Am J Physiol1995;269:G692-8

[125]

Menger MD,Messmer K.in vivo fluorescence microscopy for quantitative analysis of the hepatic microcirculation in hamsters and rats.Eur Surg Res1991;23:158-69

[126]

Miyazaki S,Kitamura A,Yamazaki Y.Investigation on the optimal position for the quantification of hepatic perfusion by use of dynamic contrast-enhanced computed tomography in rats.Radiol Phys Technol2009;2:183-188

[127]

Alexis F,Molnar LK.Factors affecting the clearance and biodistribution of polymeric nanoparticles.Mol Pharm2008;5:505-15 PMCID:PMC2663893

[128]

Watson DC,Srivatsan A.Efficient production and enhanced tumor delivery of engineered extracellular vesicles.Biomaterials2016;105:195-205 PMCID:PMC7156278

[129]

Matsumoto A,Nishikawa M.Role of phosphatidylserine-derived negative surface charges in the recognition and uptake of intravenously injected B16BL6-derived exosomes by macrophages.J Pharm Sci2017;106:168-75

[130]

Tóth ,Visnovitz T.Formation of a protein corona on the surface of extracellular vesicles in blood plasma.J Extracell Vesicles2021;10:e12140

[131]

Ezzat K,Pålsson S.The viral protein corona directs viral pathogenesis and amyloid aggregation.Nat Commun2019;10:2331

[132]

Bushey RT,Campa MJ.Complement factor H protects tumor cell-derived exosomes from complement-dependent lysis and phagocytosis.PLoS One2021;16:e0252577 PMCID:PMC8208531

[133]

Yue B.Biology of the extracellular matrix: an overview.J Glaucoma2014;23:S20-3 PMCID:PMC4185430

[134]

Dolega ME,Brunel B,Recho P.Extracellular matrix in multicellular aggregates acts as a pressure sensor controlling cell proliferation and motility.Elife2021;10 PMCID:PMC8064752

[135]

Engin AB,Neagu M.Mechanistic understanding of nanoparticles’ interactions with extracellular matrix: the cell and immune system.Part Fibre Toxicol2017;14:22 PMCID:PMC5483305

[136]

Young JL,Spatz JP.Nanoscale and mechanical properties of the physiological cell-ECM microenvironment.Exp Cell Res2016;343:3-6

[137]

Stylianopoulos T,Insin N.Diffusion of particles in the extracellular matrix: the effect of repulsive electrostatic interactions.Biophys J2010;99:1342-9 PMCID:PMC2931749

[138]

Munir MU.Nanomedicine penetration to tumor: challenges, and advanced strategies to tackle this issue.Cancers (Basel)2022;14:2904 PMCID:PMC9221319

[139]

Sanderson RD,Vlodavsky I.Proteases and glycosidases on the surface of exosomes: Newly discovered mechanisms for extracellular remodeling.Matrix Biol2019;75-76:160-9 PMCID:PMC5920797

[140]

Thompson CA,Ramani VC,Sanderson RD.Heparanase regulates secretion, composition, and function of tumor cell-derived exosomes.J Biol Chem2013;288:10093-9 PMCID:PMC3617250

[141]

Baietti MF,Mortier E.Syndecan-syntenin-ALIX regulates the biogenesis of exosomes.Nat Cell Biol2012;14:677-85

[142]

Han KY,Azar DT.MMP14-containing exosomes cleave VEGFR1 and promote VEGFA-induced migration and proliferation of vascular endothelial cells.Invest Ophthalmol Vis Sci2019;60:2321-9 PMCID:PMC6532701

[143]

Lenzini S,Chung G.Matrix mechanics and water permeation regulate extracellular vesicle transport.Nat Nanotechnol2020;15:217-23 PMCID:PMC7075670

[144]

Mohan V,Sagi I.Emerging roles of ECM remodeling processes in cancer.Semin Cancer Biol2020;62:192-200

[145]

Høye AM.Structural ECM components in the premetastatic and metastatic niche.Am J Physiol Cell Physiol2016;310:C955-67

[146]

Gaudet AD.Extracellular matrix regulation of inflammation in the healthy and injured spinal cord.Exp Neurol2014;258:24-34 PMCID:PMC4099942

[147]

Heusermann W,Trojer D.Exosomes surf on filopodia to enter cells at endocytic hot spots, traffic within endosomes, and are targeted to the ER.J Cell Biol2016;213:173-84 PMCID:PMC5084269

[148]

van Dongen HM,Witwer KW.Extracellular vesicles exploit viral entry routes for cargo delivery.Microbiol Mol Biol Rev2016;80:369-86 PMCID:PMC4867369

[149]

Bonsergent E,Buchrieser J,Théry C.Quantitative characterization of extracellular vesicle uptake and content delivery within mammalian cells.Nat Commun2021;12:1864 PMCID:PMC7994380

[150]

Durak-Kozica M,Kubat K.3D visualization of extracellular vesicle uptake by endothelial cells.Cell Mol Biol Lett2018;23:57 PMCID:PMC6296015

[151]

Hoshino A,Shen TL.Tumour exosome integrins determine organotropic metastasis.Nature2015;527:329-35

[152]

Christianson HC,van Kuppevelt TH,Belting M.Cancer cell exosomes depend on cell-surface heparan sulfate proteoglycans for their internalization and functional activity.Proc Natl Acad Sci USA2013;110:17380-5 PMCID:PMC3808637

[153]

Rana S,Stadel D.Toward tailored exosomes: the exosomal tetraspanin web contributes to target cell selection.Int J Biochem Cell Biol2012;44:1574-84

[154]

Hao S,Li F,Laferte S.Mature dendritic cells pulsed with exosomes stimulate efficient cytotoxic T-lymphocyte responses and antitumour immunity.Immunology2007;120:90-102 PMCID:PMC2265880

[155]

Miyanishi M,Koike M,Kitamura T.Identification of Tim4 as a phosphatidylserine receptor.Nature2007;450:435-9

[156]

Prada I.Binding and fusion of extracellular vesicles to the plasma membrane of their cell targets.Int J Mol Sci2016;17:1296 PMCID:PMC5000693

[157]

Hung ME.A platform for actively loading cargo RNA to elucidate limiting steps in EV-mediated delivery.J Extracell Vesicles2016;5:31027 PMCID:PMC4870355

[158]

Somiya M.Reporter gene assay for membrane fusion of extracellular vesicles.J Extracell Vesicles2021;10:e12171 PMCID:PMC8607979

[159]

Somiya M.Real-time luminescence assay for cytoplasmic cargo delivery of extracellular vesicles.Anal Chem2021;93:5612-20

[160]

Joshi BS,Giepmans BNG.Endocytosis of extracellular vesicles and release of their cargo from endosomes.ACS Nano2020;14:4444-55 PMCID:PMC7199215

[161]

Kojima R,Rizzi G.Designer exosomes produced by implanted cells intracerebrally deliver therapeutic cargo for Parkinson’s disease treatment.Nat Commun2018;9:1305 PMCID:PMC5880805

[162]

Yim N,Choi K.Exosome engineering for efficient intracellular delivery of soluble proteins using optically reversible protein-protein interaction module.Nat Commun2016;7:12277 PMCID:PMC4961865

[163]

Wang Q,Kadungure T,Zhang H.ARMMs as a versatile platform for intracellular delivery of macromolecules.Nat Commun2018;9:960 PMCID:PMC5840177

[164]

Fu B,Liu D.Endogenous retroviruses function as gene expression regulatory elements during mammalian pre-implantation embryo development.Int J Mol Sci2019;20:790 PMCID:PMC6387303

[165]

Uygur B,Arakelyan A,Chernomordik LV.Syncytin 1 dependent horizontal transfer of marker genes from retrovirally transduced cells.Sci Rep2019;9:17637 PMCID:PMC6881383

[166]

Vargas A,Éthier-Chiasson M.Syncytin proteins incorporated in placenta exosomes are important for cell uptake and show variation in abundance in serum exosomes from patients with preeclampsia.FASEB J2014;28:3703-19

[167]

Lokossou AG,Nguyen PT.Endogenous retrovirus-encoded Syncytin-2 contributes to exosome-mediated immunosuppression of T cells.Biol Reprod2020;102:185-98

[168]

Perrin P,Janssen H.Retrofusion of intralumenal MVB membranes parallels viral infection and coexists with exosome release.Curr Biol2021;31:3884-3893.e4 PMCID:PMC8445322

[169]

Sosale NG,Tsai RK.“Marker of Self” CD47 on lentiviral vectors decreases macrophage-mediated clearance and increases delivery to SIRPA-expressing lung carcinoma tumors.Mol Ther Methods Clin Dev2016;3:16080 PMCID:PMC5148596

[170]

Kamerkar S,Sugimoto H.Exosomes facilitate therapeutic targeting of oncogenic KRAS in pancreatic cancer.Nature2017;546:498-503 PMCID:PMC5538883

[171]

Belhadj Z,Deng H.A combined “eat me/don’t eat me” strategy based on extracellular vesicles for anticancer nanomedicine.J Extracell Vesicles2020;9:1806444 PMCID:PMC7480498

[172]

Cheng L,Tang J,Liu J.Gene-engineered exosomes-thermosensitive liposomes hybrid nanovesicles by the blockade of CD47 signal for combined photothermal therapy and cancer immunotherapy.Biomaterials2021;275:120964

[173]

Clayton A,Court J,Morgan BP.Antigen-presenting cell exosomes are protected from complement-mediated lysis by expression of CD55 and CD59.Eur J Immunol2003;33:522-31

[174]

Sleep D,Evans LR.Albumin as a versatile platform for drug half-life extension.Biochim Biophys Acta2013;1830:5526-34

[175]

Liang X,Galli V.Extracellular vesicles engineered to bind albumin demonstrate extended circulation time and lymph node accumulation in mouse models.J Extracell Vesicles2022;11:e12248 PMCID:PMC9314316

[176]

Suk JS,Kim N,Ensign LM.PEGylation as a strategy for improving nanoparticle-based drug and gene delivery.Adv Drug Deliv Rev2016;99:28-51 PMCID:PMC4798869

[177]

Mitchell MJ,Haley RM,Peppas NA.Engineering precision nanoparticles for drug delivery.Nat Rev Drug Discov2021;20:101-24 PMCID:PMC7717100

[178]

Patras L,Munteanu C.Trojan horse treatment based on PEG-coated extracellular vesicles to deliver doxorubicin to melanoma in vitro and in vivo.Cancer Biol Ther2022;23:1-16

[179]

Bittner B,Schmidt J.Subcutaneous administration of biotherapeutics: an overview of current challenges and opportunities.BioDrugs2018;32:425-40 PMCID:PMC6182494

[180]

Turner MR.Challenges and opportunities for the subcutaneous delivery of therapeutic proteins.J Pharm Sci2018;107:1247-60 PMCID:PMC5915922

[181]

Al Shoyaib A,Karamyan VT.Intraperitoneal route of drug administration: should it be used in experimental animal studies?.Pharm Res2019;37:12 PMCID:PMC7412579

[182]

Jafarnejad M,Zawieja DC,Moore JE Jr.Modeling lymph flow and fluid exchange with blood vessels in lymph nodes.Lymphat Res Biol2015;13:234-47 PMCID:PMC4685511

[183]

Driedonks T,Carlson B.Pharmacokinetics and biodistribution of extracellular vesicles administered intravenously and intranasally to Macaca nemestrina.J Extracell Biol2022;1:e59

[184]

Banks WA,Bullock KM,Ludwig N.Transport of extracellular vesicles across the blood-brain barrier: brain pharmacokinetics and effects of inflammation.Int J Mol Sci2020;21:4407 PMCID:PMC7352415

[185]

Ferreira JV,Ramalho J.LAMP2A regulates the loading of proteins into exosomes.Sci Adv2022;8:1140 PMCID:PMC8956266

[186]

Kim G,Lee Y,Hwang DW.Systemic delivery of microRNA-21 antisense oligonucleotides to the brain using T7-peptide decorated exosomes.J Control Release2020;317:273-81

[187]

Tian Y,Song J.A doxorubicin delivery platform using engineered natural membrane vesicle exosomes for targeted tumor therapy.Biomaterials2014;35:2383-90

[188]

Bai J,Liu R.Engineered targeting tLyp-1 exosomes as gene therapy vectors for efficient delivery of siRNA into lung cancer cells.Asian J Pharm Sci2020;15:461-71 PMCID:PMC7486479

[189]

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

[190]

Choi H,Kim DH.Strategies for targeted delivery of exosomes to the brain: advantages and challenges.Pharmaceutics2022;14:672 PMCID:PMC8948948

[191]

Liang G,Zhu Y,Feng W.Engineered exosome-mediated delivery of functionally active miR-26a and its enhanced suppression effect in HepG2 cells.Int J Nanomedicine2018;13:585-99 PMCID:PMC5796471

[192]

Wang JH,Zhao J.Anti-HER2 scFv-directed extracellular vesicle-mediated mRNA-based gene delivery inhibits growth of HER2-positive human breast tumor xenografts by prodrug activation.Mol Cancer Ther2018;17:1133-42

[193]

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

[194]

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

[195]

Choi H,Yim HY,Yoo JK.Biodistribution of Exosomes and Engineering Strategies for Targeted Delivery of Therapeutic Exosomes.Tissue Eng Regen Med2021;18:499-511 PMCID:PMC8325750

[196]

Rivoltini L,Squarcina P.TNF-related apoptosis-inducing ligand (TRAIL)-armed exosomes deliver proapoptotic signals to tumor site.Clin Cancer Res2016;22:3499-512

[197]

Zheng W,Liang X.Cell-specific targeting of extracellular vesicles though engineering the glycocalyx.J Extracell Vesicles2022;11:e12290 PMCID:PMC9719568

[198]

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

[199]

Tian T,He CP.Surface functionalized exosomes as targeted drug delivery vehicles for cerebral ischemia therapy.Biomaterials2018;150:137-49

[200]

Jia G,An Y.NRP-1 targeted and cargo-loaded exosomes facilitate simultaneous imaging and therapy of glioma in vitro and in vivo.Biomaterials2018;178:302-16

[201]

Wang Y,Tian B.Nucleolin-targeted extracellular vesicles as a versatile platform for biologics delivery to breast cancer.Theranostics2017;7:1360-72 PMCID:PMC5399599

[202]

Pi F,Lee TJ.Nanoparticle orientation to control RNA loading and ligand display on extracellular vesicles for cancer regression.Nat Nanotechnol2018;13:82-9 PMCID:PMC5762263

[203]

Li L,Guo Q.Exosome-liposome hybrid nanoparticle codelivery of TP and miR497 conspicuously overcomes chemoresistant ovarian cancer.J Nanobiotechnology2022;20:50 PMCID:PMC8787930

AI Summary AI Mindmap
PDF

109

Accesses

0

Citation

Detail

Sections
Recommended

AI思维导图

/