Abstract
Drug delivery systems are created to achieve the desired therapeutic effect of a specific pharmaceutical compound. Numerous drawbacks and side effects such as unfavorable pharmacokinetics, lack of tissue selectivity, immunogenicity, increased systemic clearance and toxicity, have been observed for currently available drug delivery systems (DDSs). The use of natural and artificial extracellular vesicles (EVs) in drug delivery may help to solve the aforementioned problems faced by different DDSs. Due to their self-origin, small size, flexibility, the presence of multiple adhesive molecules on their surfaces as well as their function as biomolecules carriers, EVs are the perfect candidates for DDSs. Currently, several drug delivery systems based on EVs have been proposed. While the great potential of these particles in targeted drug delivery has been recognized in cancer, hepatitis C, neurodegenerative diseases, inflammatory states etc., this field is still in the early stage of development. Unfortunately, the use of EVs from natural sources (cell cultures, body fluids) results in numerous problems in terms of the heterogeneity of isolated vesicle population as well as the method of isolation thereof, which may influence vesicle composition and properties. Therefore, there is a significant need for the synthesis of artificial EV-based DDSs under strictly controlled laboratory conditions and from well-defined biomolecules (proteins and lipids). Vesicle-mimetic delivery systems, characterized by properties similar to natural EVs, will bring new opportunities to study the mechanisms of DDS internalization and their biological activity after delivering their cargo to a target cell.
Keywords: Drug loading, ectosomes, exosomes, liposomes, microvesicles, drug delivery systems.
[1]
Park K. Controlled drug delivery systems: Past forward and future back. J Control Release 2014; 190: 3-8.
[2]
Mahmoudi M, Lynch I, Ejtehadi MR, Monopoli MP, Bombelli FB, Laurent S. Protein-nanoparticle interactions: Opportunities and challenges. Chem Rev 2011; 111(9): 5610-37.
[3]
Crommelin DJ, Florence AT. Towards more effective advanced drug delivery systems. Int J Pharm 2013; 454(1): 496-511.
[4]
Jain KK. Current status and future prospects of drug delivery systems. Methods Mol Biol 2014; 1141: 1-56.
[5]
Tian Y, Li S, Song J, et al. A doxorubicin delivery platform using engineered natural membrane vesicle exosomes for targeted tumor therapy. Biomaterials 2014; 35(7): 2383-90.
[6]
Heidegger S, Gössl D, Schmidt A, et al. Immune response to functionalized mesoporous silica nanoparticles for targeted drug delivery. Nanoscale 2016; 8(2): 938-48.
[7]
Obarzanek-Fojt M, Curdy C, Loggia N, et al. Tracking immune-related cell responses to drug delivery microparticles in 3D dense collagen matrix. Eur J Pharm Biopharm 2016; 107: 180-90.
[8]
Hamidi M, Azadi A, Rafiei P, Ashrafi H. A pharmacokinetic overview of nanotechnology-based drug delivery systems: An ADME-oriented approach. Crit Rev Ther Drug Carrier Syst 2013; 30(5): 435-67.
[9]
van Niel G, D’Angelo G, Raposo G. Shedding light on the cell biology of extracellular vesicles. Nat Rev Mol Cell Biol 2018; 19(4): 213-28.
[10]
Lo Cicero A, Stahl PD, Raposo G. Extracellular vesicles shuffling intercellular messages: for good or for bad. Curr Opin Cell Biol 2015; 35: 69-77.
[11]
Raposo G, Stoorvogel W. Extracellular vesicles: Exosomes, microvesicles, and friends. J Cell Biol 2013; 200(4): 373-83.
[12]
Wang Y, Chen X, Tian B, et al. Nucleolin-targeted extracellular vesicles as a versatile platform for biologics delivery to breast cancer. Theranostics 2017; 7(5): 1360-72.
[13]
Aqil F, Kausar H, Agrawal AK, et al. Exosomal formulation enhances therapeutic response of celastrol against lung cancer. Exp Mol Pathol 2016; 101(1): 12-21.
[14]
Agrawal AK, Aqil F, Jeyabalan J, et al. Milk-derived exosomes for oral delivery of paclitaxel. Nanomedicine (Lond) 2017; 13(5): 1627-36.
[15]
Yuana Y, Sturk A, Nieuwland R. Extracellular vesicles in physiological and pathological conditions. Blood Rev 2013; 27(1): 31-9.
[16]
Bobrie A, Colombo M, Krumeich S, Raposo G, Théry C. Diverse subpopulations of vesicles secreted by different intracellular mechanisms are present in exosome preparations obtained by differential ultracentrifugation. J Extracell Vesicles 2012; 1: 1.
[17]
Xu R, Greening DW, Rai A, Ji H, Simpson RJ. Highly-purified exosomes and shed microvesicles isolated from the human colon cancer cell line LIM1863 by sequential centrifugal ultrafiltration are biochemically and functionally distinct. Methods 2015; 87: 11-25.
[18]
Böing AN, van der Pol E, Grootemaat AE, Coumans FA, Sturk A, Nieuwland R. Single-step isolation of extracellular vesicles by size-exclusion chromatography. J Extracell Vesicles 2014; 3: 1.
[19]
Nordin JZ, Lee Y, Vader P, et al. Ultrafiltration with size-exclusion liquid chromatography for high yield isolation of extracellular vesicles preserving intact biophysical and functional properties. Nanomedicine (Lond) 2015; 11(4): 879-83.
[20]
Yamashita T, Takahashi Y, Nishikawa M, Takakura Y. Effect of exosome isolation methods on physicochemical properties of exosomes and clearance of exosomes from the blood circulation. Eur J Pharm Biopharm 2016; 98: 1-8.
[21]
Kim DK, Lee J, Kim SR, et al. EVpedia: a community web portal for extracellular vesicles research. Bioinformatics 2015; 31(6): 933-9.
[22]
van der Pol E, Böing AN, Harrison P, Sturk A, Nieuwland R. Classification, functions, and clinical relevance of extracellular vesicles. Pharmacol Rev 2012; 64(3): 676-705.
[23]
Savina A, Fader CM, Damiani MT, Colombo MI. Rab11 promotes docking and fusion of multivesicular bodies in a calcium-dependent manner. Traffic 2005; 6(2): 131-43.
[24]
Hsu C, Morohashi Y, Yoshimura S, et al. Regulation of exosome secretion by Rab35 and its GTPase-activating proteins TBC1D10A-C. J Cell Biol 2010; 189(2): 223-32.
[25]
Ostrowski M, Carmo NB, Krumeich S, et al. Rab27a and Rab27b control different steps of the exosome secretion pathway. Nat Cell Biol 2010; 12(1): 19-30. 1-13.
[26]
Savina A, Furlán M, Vidal M, Colombo MI. Exosome release is regulated by a calcium-dependent mechanism in K562 cells. J Biol Chem 2003; 278(22): 20083-90.
[27]
Loomis RJ, Holmes DA, Elms A, Solski PA, Der CJ, Su L. Citron kinase, a RhoA effector, enhances HIV-1 virion production by modulating exocytosis. Traffic 2006; 7(12): 1643-53.
[28]
Rao SK, Huynh C, Proux-Gillardeaux V, Galli T, Andrews NW. Identification of SNAREs involved in synaptotagmin VII-regulated lysosomal exocytosis. J Biol Chem 2004; 279(19): 20471-9.
[29]
Booth AM, Fang Y, Fallon JK, Yang JM, Hildreth JE, Gould SJ. Exosomes and HIV Gag bud from endosome-like domains of the T cell plasma membrane. J Cell Biol 2006; 172(6): 923-35.
[30]
Lenassi M, Cagney G, Liao M, et al. HIV Nef is secreted in exosomes and triggers apoptosis in bystander CD4+ T cells. Traffic 2010; 11(1): 110-22.
[31]
Fang Y, Wu N, Gan X, Yan W, Morrell JC, Gould SJ. Higher-order oligomerization targets plasma membrane proteins and HIV gag to exosomes. PLoS Biol 2007; 5(6)e158
[32]
Heijnen HF, Schiel AE, Fijnheer R, Geuze HJ, Sixma JJ. Activated platelets release two types of membrane vesicles: microvesicles by surface shedding and exosomes derived from exocytosis of multivesicular bodies and alpha-granules. Blood 1999; 94(11): 3791-9.
[33]
Katzmann DJ, Babst M, Emr SD. Ubiquitin-dependent sorting into the multivesicular body pathway requires the function of a conserved endosomal protein sorting complex, ESCRT-I. Cell 2001; 106(2): 145-55.
[34]
Buschow SI, Liefhebber JM, Wubbolts R, Stoorvogel W. Exosomes contain ubiquitinated proteins. Blood Cells Mol Dis 2005; 35(3): 398-403.
[35]
Buschow SI, Nolte-’t Hoen EN, van Niel G, et al. MHC II in dendritic cells is targeted to lysosomes or T cell-induced exosomes via distinct multivesicular body pathways. Traffic 2009; 10(10): 1528-42.
[36]
Tamai K, Tanaka N, Nakano T, et al. Exosome secretion of dendritic cells is regulated by Hrs, an ESCRT-0 protein. Biochem Biophys Res Commun 2010; 399(3): 384-90.
[39]
Trajkovic K, Hsu C, Chiantia S, et al. Ceramide triggers budding of exosome vesicles into multivesicular endosomes. Science 2008; 319(5867): 1244-7.
[40]
Morel O, Jesel L, Freyssinet JM, Toti F. Cellular mechanisms underlying the formation of circulating microparticles. Arterioscler Thromb Vasc Biol 2011; 31(1): 15-26.
[41]
Surman M, Stępień E, Hoja-Łukowicz D, Przybyło M. Deciphering the role of ectosomes in cancer development and progression: Focus on the proteome. Clin Exp Metastasis 2017; 34(3-4): 273-89.
[42]
Li B, Antonyak MA, Zhang J, Cerione RA. RhoA triggers a specific signaling pathway that generates transforming microvesicles in cancer cells. Oncogene 2012; 31(45): 4740-9.
[43]
Muralidharan-Chari V, Clancy J, Plou C, et al. ARF6-regulated shedding of tumor cell-derived plasma membrane microvesicles. Curr Biol 2009; 19(22): 1875-85.
[44]
Wickman G, Julian L, Olson MF. How apoptotic cells aid in the removal of their own cold dead bodies. Cell Death Differ 2012; 19(5): 735-42.
[45]
Sebbagh M, Renvoizé C, Hamelin J, Riché N, Bertoglio J, Bréard J. Caspase-3-mediated cleavage of ROCK I induces MLC phosphorylation and apoptotic membrane blebbing. Nat Cell Biol 2001; 3(4): 346-52.
[46]
Jänicke RU, Sprengart ML, Wati MR, Porter AG. Caspase-3 is required for DNA fragmentation and morphological changes associated with apoptosis. J Biol Chem 1998; 273(16): 9357-60.
[47]
Taylor DD, Akyol S, Gercel-Taylor C. Pregnancy-associated exosomes and their modulation of T cell signaling. J Immunol 2006; 176(3): 1534-42.
[48]
Hedlund M, Stenqvist AC, Nagaeva O, et al. Human placenta expresses and secretes NKG2D ligands via exosomes that down-modulate the cognate receptor expression: Evidence for immunosuppressive function. J Immunol 2009; 183(1): 340-51.
[49]
Kim JW, Wieckowski E, Taylor DD, Reichert TE, Watkins S, Whiteside TL. Fas ligand-positive membranous vesicles isolated from sera of patients with oral cancer induce apoptosis of activated T lymphocytes. Clin Cancer Res 2005; 11(3): 1010-20.
[50]
Liu Y, Xiang X, Zhuang X, et al. Contribution of MyD88 to the tumor exosome-mediated induction of myeloid derived suppressor cells. Am J Pathol 2010; 176(5): 2490-9.
[51]
Baj-Krzyworzeka M, Mytar B, Szatanek R, et al. Colorectal cancer-derived microvesicles modulate differentiation of human monocytes to macrophages. J Transl Med 2016; 14: 36.
[52]
Flanagan J, Middeldorp J, Sculley T. Localization of the Epstein-Barr virus protein LMP 1 to exosomes. J Gen Virol 2003; 84(Pt 7): 1871-9.
[53]
Silverman JM, Clos J, Horakova E, et al. Leishmania exosomes modulate innate and adaptive immune responses through effects on monocytes and dendritic cells. J Immunol 2010; 185(9): 5011-22.
[54]
Zhang HG, Liu C, Su K, et al. A membrane form of TNF-alpha presented by exosomes delays T cell activation-induced cell death. J Immunol 2006; 176(12): 7385-93.
[55]
Admyre C, Bohle B, Johansson SM, et al. B cell-derived exosomes can present allergen peptides and activate allergen-specific T cells to proliferate and produce TH2-like cytokines. J Allergy Clin Immunol 2007; 120(6): 1418-24.
[56]
Bakhti M, Winter C, Simons M. Inhibition of myelin membrane sheath formation by oligodendrocyte-derived exosome-like vesicles. J Biol Chem 2011; 286(1): 787-96.
[57]
Wang S, Cesca F, Loers G, et al. Synapsin I is an oligomannose-carrying glycoprotein, acts as an oligomannose-binding lectin, and promotes neurite outgrowth and neuronal survival when released via glia-derived exosomes. J Neurosci 2011; 31(20): 7275-90.
[58]
Chivet M, Javalet C, Laulagnier K, Blot B, Hemming FJ, Sadoul R. Exosomes secreted by cortical neurons upon glutamatergic synapse activation specifically interact with neurons. J Extracell Vesicles 2014; 3: 24722.
[59]
Frühbeis C, Fröhlich D, Kuo WP, et al. Neurotransmitter-triggered transfer of exosomes mediates oligodendrocyte-neuron communication. PLoS Biol 2013; 11(7)e1001604
[60]
Coleman BM, Hill AF. Extracellular vesicles--Their role in the packaging and spread of misfolded proteins associated with neurodegenerative diseases. Semin Cell Dev Biol 2015; 40: 89-96.
[61]
Barile L, Lionetti V, Cervio E, et al. Extracellular vesicles from human cardiac progenitor cells inhibit cardiomyocyte apoptosis and improve cardiac function after myocardial infarction. Cardiovasc Res 2014; 103(4): 530-41.
[62]
Yu B, Gong M, Wang Y, et al. Cardiomyocyte protection by GATA-4 gene engineered mesenchymal stem cells is partially mediated by translocation of miR-221 in microvesicles. PLoS One 2013; 8(8)e73304
[63]
Lopez-Verrilli MA, Picou F, Court FA. Schwann cell-derived exosomes enhance axonal regeneration in the peripheral nervous system. Glia 2013; 61(11): 1795-806.
[64]
Furuta T, Miyaki S, Ishitobi H, et al. Mesenchymal stem cell-derived exosomes promote fracture healing in a mouse model. Stem Cells Transl Med 2016; 5(12): 1620-30.
[65]
Zhang J, Guan J, Niu X, et al. Exosomes released from human induced pluripotent stem cells-derived MSCs facilitate cutaneous wound healing by promoting collagen synthesis and angiogenesis. J Transl Med 2015; 13: 49.
[66]
Berckmans RJ, Sturk A, van Tienen LM, Schaap MC, Nieuwland R. Cell-derived vesicles exposing coagulant tissue factor in saliva. Blood 2011; 117(11): 3172-80.
[67]
Zwicker JI, Liebman HA, Neuberg D, et al. Tumor-derived tissue factor-bearing microparticles are associated with venous thromboembolic events in malignancy. Clin Cancer Res 2009; 15(22): 6830-40.
[68]
Hugel B, Socié G, Vu T, et al. Elevated levels of circulating procoagulant microparticles in patients with paroxysmal nocturnal hemoglobinuria and aplastic anemia. Blood 1999; 93(10): 3451-6.
[69]
Mallat Z, Benamer H, Hugel B, et al. Elevated levels of shed membrane microparticles with procoagulant potential in the peripheral circulating blood of patients with acute coronary syndromes. Circulation 2000; 101(8): 841-3.
[70]
Mallat Z, Hugel B, Ohan J, Lesèche G, Freyssinet JM, Tedgui A. Shed membrane microparticles with procoagulant potential in human atherosclerotic plaques: A role for apoptosis in plaque thrombogenicity. Circulation 1999; 99(3): 348-53.
[71]
Nieuwland R, Berckmans RJ, Rotteveel-Eijkman RC, et al. Cell-derived microparticles generated in patients during cardiopulmonary bypass are highly procoagulant. Circulation 1997; 96(10): 3534-41.
[72]
Nieuwland R, Berckmans RJ, McGregor S, et al. Cellular origin and procoagulant properties of microparticles in meningococcal sepsis. Blood 2000; 95(3): 930-5.
[73]
Berckmans RJ, Nieuwland R, Tak PP, et al. Cell-derived microparticles in synovial fluid from inflamed arthritic joints support coagulation exclusively via a factor VII-dependent mechanism. Arthritis Rheum 2002; 46(11): 2857-66.
[74]
Furie B, Furie BC. Role of platelet P-selectin and microparticle PSGL-1 in thrombus formation. Trends Mol Med 2004; 10(4): 171-8.
[75]
Del Conde I, Shrimpton CN, Thiagarajan P, López JA. Tissue-factor-bearing microvesicles arise from lipid rafts and fuse with activated platelets to initiate coagulation. Blood 2005; 106(5): 1604-11.
[76]
Dachary-Prigent J, Pasquet JM, Fressinaud E, Toti F, Freyssinet JM, Nurden AT. Aminophospholipid exposure, microvesiculation and abnormal protein tyrosine phosphorylation in the platelets of a patient with Scott syndrome: A study using physiologic agonists and local anaesthetics. Br J Haematol 1997; 99(4): 959-67.
[77]
Shimoda M, Khokha R. Metalloproteinases in extracellular vesicles. Biochim Biophys Acta Mol Cell Res 2017; 1864(11 Pt A): 1989-2000.
[78]
Kim HK, Song KS, Chung JH, Lee KR, Lee SN. Platelet microparticles induce angiogenesis in vitro. Br J Haematol 2004; 124(3): 376-84.
[79]
Ribeiro-Rodrigues TM, Laundos TL, Pereira-Carvalho R, et al. Exosomes secreted by cardiomyocytes subjected to ischaemia promote cardiac angiogenesis. Cardiovasc Res 2017; 113(11): 1338-50.
[80]
Brill A, Dashevsky O, Rivo J, Gozal Y, Varon D. Platelet-derived microparticles induce angiogenesis and stimulate post-ischemic revascularization. Cardiovasc Res 2005; 67(1): 30-8.
[81]
Abid Hussein MN, Nieuwland R, Hau CM, Evers LM, Meesters EW, Sturk A. Cell-derived microparticles contain caspase 3 in vitro and in vivo. J Thromb Haemost 2005; 3(5): 888-96.
[82]
Tourneur L, Mistou S, Schmitt A, Chiocchia G. Adenosine receptors control a new pathway of Fas-associated death domain protein expression regulation by secretion. J Biol Chem 2008; 283(26): 17929-38.
[83]
Al-Nedawi K, Meehan B, Micallef J, et al. Intercellular transfer of the oncogenic receptor EGFRvIII by microvesicles derived from tumour cells. Nat Cell Biol 2008; 10(5): 619-24.
[84]
Endo-Munoz L, Cai N, Cumming A, et al. Progression of osteosarcoma from a non-metastatic to a metastatic phenotype is causally associated with activation of an autocrine and paracrine uPA axis. PLoS One 2015; 10(8)e0133592
[85]
Taraboletti G, D’Ascenzo S, Giusti I, et al. Bioavailability of VEGF in tumor-shed vesicles depends on vesicle burst induced by acidic pH. Neoplasia 2006; 8(2): 96-103.
[86]
Liu Y, Zhu XJ, Zeng C, et al. Microvesicles secreted from human multiple myeloma cells promote angiogenesis. Acta Pharmacol Sin 2014; 35(2): 230-8.
[87]
Yamada N, Tsujimura N, Kumazaki M, et al. Colorectal cancer cell-derived microvesicles containing microRNA-1246 promote angiogenesis by activating Smad 1/5/8 signaling elicited by PML down-regulation in endothelial cells. Biochim Biophys Acta 2014; 1839(11): 1256-72.
[88]
Köppler B, Cohen C, Schlöndorff D, Mack M. Differential mechanisms of microparticle transfer toB cells and monocytes: anti-inflammatory propertiesof microparticles. Eur J Immunol 2006; 36(3): 648-60.
[89]
Valenti R, Huber V, Filipazzi P, et al. Human tumor-released microvesicles promote the differentiation of myeloid cells with transforming growth factor-beta-mediated suppressive activity on T lymphocytes. Cancer Res 2006; 66(18): 9290-8.
[90]
Bebawy M, Combes V, Lee E, et al. Membrane microparticles mediate transfer of P-glycoprotein to drug sensitive cancer cells. Leukemia 2009; 23(9): 1643-9.
[91]
Lu JF, Luk F, Gong J, Jaiswal R, Grau GE, Bebawy M. Microparticles mediate MRP1 intercellular transfer and the re-templating of intrinsic resistance pathways. Pharmacol Res 2013; 76: 77-83.
[92]
Shedden K, Xie XT, Chandaroy P, Chang YT, Rosania GR. Expulsion of small molecules in vesicles shed by cancer cells: association with gene expression and chemosensitivity profiles. Cancer Res 2003; 63(15): 4331-7.
[93]
Chen B, Li Q, Zhao B, Wang Y. Stem cell-derived extracellular vesicles as a novel potential therapeutic tool for tissue repair. Stem Cells Transl Med 2017; 6(9): 1753-8.
[94]
Yang C, Mwaikambo BR, Zhu T, et al. Lymphocytic microparticles inhibit angiogenesis by stimulating oxidative stress and negatively regulating VEGF-induced pathways. Am J Physiol Regul Integr Comp Physiol 2008; 294(2): R467-76.
[95]
Baj-Krzyworzeka M, Szatanek R, Weglarczyk K, Baran J, Zembala M. Tumour-derived microvesicles modulate biological activity of human monocytes. Immunol Lett 2007; 113(2): 76-82.
[96]
Van Deun J, Mestdagh P, Sormunen R, et al. The impact of disparate isolation methods for extracellular vesicles on downstream RNA profiling. J Extracell Vesicles 2014; 3: 1-14.
[97]
Taylor DD, Shah S. Methods of isolating extracellular vesicles impact down-stream analyses of their cargoes. Methods 2015; 87: 3-10.
[98]
Cvjetkovic A, Lötvall J, Lässer C. The influence of rotor type and centrifugation time on the yield and purity of extracellular vesicles. J Extracell Vesicles 2014; 3: 1-11.
[99]
Taylor DD, Shah S. Methods of isolating extracellular vesicles impact down-stream analyses of their cargoes. Methods 2015; 87: 3-10.
[100]
Yuana Y, Levels J, Grootemaat A, Sturk A, Nieuwland R. Co-isolation of extracellular vesicles and high-density lipoproteins using density gradient ultracentrifugation. J Extracell Vesicles 2014; 3: 1.
[101]
Théry C, Clayton A, Amigorena S, Raposo G. Isolation and characterization of exosomes from cell culture supernatants. Cell Biol 2006; 3: 1-29.
[102]
Konoshenko MY, Lekchnov EA, Vlassov AV, Laktionov PP. Isolation of extracellular vesicles: general methodologies and latest trends. BioMed Res Int 2018; 20188545347
[103]
Witwer KW, Buzás EI, Bemis LT, et al. Standardization of sample collection, isolation and analysis methods in extracellular vesicle research. J Extracell Vesicles 2013; 2: 1.
[104]
Ghosh A, Davey M, Chute IC, et al. Rapid isolation of extracellular vesicles from cell culture and biological fluids using a synthetic peptide with specific affinity for heat shock proteins. PLoS One 2014; 9(10)e110443
[105]
Merchant ML, Powell DW, Wilkey DW, et al. Microfiltration isolation of human urinary exosomes for characterization by MS. Proteomics Clin Appl 2010; 4(1): 84-96.
[106]
Musante L, Tataruch-Weinert D, Kerjaschki D, Henry M, Meleady P, Holthofer H. Residual urinary extracellular vesicles in ultracentrifugation supernatants after hydrostatic filtration dialysis enrichment. J Extracell Vesicles 2016; 6(1)1267896
[107]
Tataruch-Weinert D, Musante L, Kretz O, Holthofer H. Urinary extracellular vesicles for RNA extraction: optimization of a protocol devoid of prokaryote contamination. J Extracell Vesicles 2016; 5: 30281.
[108]
Verplaetse H, Verbeeck RM, Verbaeys A, Oosterlinck W. Solubility of calcium oxalate monohydrate and hydroxyapatite in EDTA solutions. J Urol 1986; 135(3): 608-11.
[109]
Momen-Heravi F, Balaj L, Alian S, et al. Current methods for the isolation of extracellular vesicles. Biol Chem 2013; 394(10): 1253-62.
[110]
Yoo CE, Kim G, Kim M, et al. A direct extraction method for microRNAs from exosomes captured by immunoaffinity beads. Anal Biochem 2012; 431(2): 96-8.
[111]
Nakai W, Yoshida T, Diez D, et al. A novel affinity-based method for the isolation of highly purified extracellular vesicles. Sci Rep 2016; 6: 33935.
[112]
Balaj L, Atai NA, Chen W, et al. Heparin affinity purification of extracellular vesicles. Sci Rep 2015; 5: 10266.
[113]
Kanchi Ravi R, Khosroheidari M, DiStefano JK. A modified precipitation method to isolate urinary exosomes. J Vis Exp 2015; 95(95): 51158.
[114]
Gámez-Valero A, Monguió-Tortajada M, Carreras-Planella L. Franquesa Ml, Beyer K, Borràs FE. Size-Exclusion Chromatography-based isolation minimally alters Extracellular Vesicles’ characteristics compared to precipitating agents. Sci Rep 2016; 6: 33641.
[115]
Grant R, Ansa-Addo E, Stratton D, et al. A filtration-based protocol to isolate human plasma membrane-derived vesicles and exosomes from blood plasma. J Immunol Methods 2011; 371(1-2): 143-51.
[116]
Cheruvanky A, Zhou H, Pisitkun T, et al. Rapid isolation of urinary exosomal biomarkers using a nanomembrane ultrafiltration concentrator. Am J Physiol Renal Physiol 2007; 292(5): F1657-61.
[117]
Musante L, Tataruch D, Gu D, et al. A simplified method to recover urinary vesicles for clinical applications, and sample banking. Sci Rep 2014; 4: 7532.
[118]
Yang Y, Hong Y, Cho E, Kim GB, Kim IS. Extracellular vesicles as a platform for membrane-associated therapeutic protein delivery. J Extracell Vesicles 2018; 7(1)1440131
[119]
Kosaka N, Iguchi H, Yoshioka Y, Takeshita F, Matsuki Y, Ochiya T. Secretory mechanisms and intercellular transfer of microRNAs in living cells. J Biol Chem 2010; 285(23): 17442-52.
[120]
Zhang Y, Liu D, Chen X, et al. Secreted monocytic miR-150 enhances targeted endothelial cell migration. Mol Cell 2010; 39(1): 133-44.
[121]
Villarroya-Beltri C, Gutiérrez-Vázquez C, Sánchez-Cabo F, et al. Sumoylated hnRNPA2B1 controls the sorting of miRNAs into exosomes through binding to specific motifs. Nat Commun 2013; 4: 2980.
[122]
Akao Y, Iio A, Itoh T, et al. Microvesicle-mediated RNA molecule delivery system using monocytes/macrophages. Mol Ther 2011; 19(2): 395-9.
[123]
Pascucci L, Coccè V, Bonomi A, et al. Paclitaxel is incorporated by mesenchymal stromal cells and released in exosomes that inhibit in vitro tumor growth: a new approach for drug delivery. J Control Release 2014; 192: 262-70.
[124]
Lv LH, Wan YL, Lin Y, et al. Anticancer drugs cause release of exosomes with heat shock proteins from human hepatocellular carcinoma cells that elicit effective natural killer cell antitumor responses in vitro. J Biol Chem 2012; 287(19): 15874-85.
[125]
Tang K, Zhang Y, Zhang H, et al. Delivery of chemotherapeutic drugs in tumour cell-derived microparticles. Nat Commun 2012; 3: 1282.
[126]
Lee J, Kim J, Jeong M, et al. Liposome-based engineering of cells to package hydrophobic compounds in membrane vesicles for tumor penetration. Nano Lett 2015; 15(5): 2938-44.
[127]
Zeelenberg IS, Ostrowski M, Krumeich S, et al. Targeting tumor antigens to secreted membrane vesicles in vivo induces efficient antitumor immune responses. Cancer Res 2008; 68(4): 1228-35.
[128]
Yim N, Ryu SW, Choi K, et al. Exosome engineering for efficient intracellular delivery of soluble proteins using optically reversible protein-protein interaction module. Nat Commun 2016; 7: 12277.
[129]
Sun D, Zhuang X, Xiang X, et al. A novel nanoparticle drug delivery system: the anti-inflammatory activity of curcumin is enhanced when encapsulated in exosomes. Mol Ther 2010; 18(9): 1606-14.
[130]
Kim MS, Haney MJ, Zhao Y, et al. Development of exosome-encapsulated paclitaxel to overcome MDR in cancer cells. Nanomedicine (Lond) 2016; 12(3): 655-64.
[131]
Alvarez-Erviti L, Seow Y, Yin H, Betts C, Lakhal S, Wood MJ. Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat Biotechnol 2011; 29(4): 341-5.
[132]
Wahlgren J, De L, Karlson T, Brisslert M, et al. Plasma exosomes can deliver exogenous short interfering RNA to monocytes and lymphocytes. Nucleic Acids Res 2012; 40(17)e130
[133]
Kooijmans SAA, Stremersch S, Braeckmans K, et al. Electroporation-induced siRNA precipitation obscures the efficiency of siRNA loading into extracellular vesicles. J Control Release 2013; 172(1): 229-38.
[134]
Hood JL, Scott MJ, Wickline SA. Maximizing exosome colloidal stability following electroporation. Anal Biochem 2014; 448: 41-9.
[135]
Didiot MC, Hall LM, Coles AH, et al. Exosome-mediated delivery of hydrophobically modified siRNA for huntingtin mRNA silencing. Mol Ther 2016; 24(10): 1836-47.
[136]
Haney MJ, Klyachko NL, Zhao Y, et al. Exosomes as drug delivery vehicles for Parkinson’s disease therapy. J Control Release 2015; 207: 18-30.
[137]
Fuhrmann G, Serio A, Mazo M, Nair R, Stevens MM. Active loading into extracellular vesicles significantly improves the cellular uptake and photodynamic effect of porphyrins. J Control Release 2015; 205: 35-44.
[138]
Wiklander OP, Nordin JZ, O’Loughlin A, et al. Extracellular vesicle in vivo biodistribution is determined by cell source, route of administration and targeting. J Extracell Vesicles 2015; 4: 26316.
[139]
Lai CP, Mardini O, Ericsson M, et al. Dynamic biodistribution of extracellular vesicles in vivo using a multimodal imaging reporter. ACS Nano 2014; 8(1): 483-94.
[140]
Bala S, Csak T, Momen-Heravi F, et al. Biodistribution and function of extracellular miRNA-155 in mice. Sci Rep 2015; 5: 10721.
[141]
Imai T, Takahashi Y, Nishikawa M, et al. Macrophage-dependent clearance of systemically administered B16BL6-derived exosomes from the blood circulation in mice. J Extracell Vesicles 2015; 4: 26238.
[142]
Clayton A, Harris CL, Court J, Mason MD, Morgan BP. Antigen-presenting cell exosomes are protected from complement-mediated lysis by expression of CD55 and CD59. Eur J Immunol 2003; 33(2): 522-31.
[143]
Whitehead B, Wu L, Hvam ML, et al. Tumour exosomes display differential mechanical and complement activation properties dependent on malignant state: Implications in endothelial leakiness. J Extracell Vesicles 2015; 4: 29685.
[144]
Kooijmans SAA, Fliervoet LAL, van der Meel R, et al. PEGylated and targeted extracellular vesicles display enhanced cell specificity and circulation time. J Control Release 2016; 224: 77-85.
[145]
Bellavia D, Raimondo S, Calabrese G, et al. Interleukin 3- receptor targeted exosomes inhibit in vitro and in vivo Chronic Myelogenous Leukemia cell growth. Theranostics 2017; 7(5): 1333-45.
[146]
Ohno S, Takanashi M, Sudo K, et al. Systemically injected exosomes targeted to EGFR deliver antitumor microRNA to breast cancer cells. Mol Ther 2013; 21(1): 185-91.
[147]
Hung ME, Leonard JN. Stabilization of exosome-targeting peptides via engineered glycosylation. J Biol Chem 2015; 290(13): 8166-72.
[148]
Kooijmans SAA, Gitz-Francois JJJM, Schiffelers RM, Vader P. Recombinant phosphatidylserine-binding nanobodies for targeting of extracellular vesicles to tumor cells: a plug-and-play approach. Nanoscale 2018; 10(5): 2413-26.
[149]
Silva AK, Luciani N, Gazeau F, et al. Combining magnetic nanoparticles with cell derived microvesicles for drug loading and targeting. Nanomedicine (Lond) 2015; 11(3): 645-55.
[150]
Aqil F, Jeyabalan J, Agrawal AK, et al. Exosomal delivery of berry anthocyanidins for the management of ovarian cancer. Food Funct 2017; 8(11): 4100-7.
[151]
Munagala R, Aqil F, Jeyabalan J, Gupta RC. Bovine milk-derived exosomes for drug delivery. Cancer Lett 2016; 371(1): 48-61.
[152]
Mizrak A, Bolukbasi MF, Ozdener GB, et al. Genetically engineered microvesicles carrying suicide mRNA/protein inhibit schwannoma tumor growth. Mol Ther 2013; 21(1): 101-8.
[153]
Zhang Y, Li L, Yu J, et al. Microvesicle-mediated delivery of transforming growth factor β1 siRNA for the suppression of tumor growth in mice. Biomaterials 2014; 35(14): 4390-400.
[154]
Pan Q, Ramakrishnaiah V, Henry S, et al. Hepatic cell-to-cell transmission of small silencing RNA can extend the therapeutic reach of RNA interference (RNAi). Gut 2012; 61(9): 1330-9.
[155]
Zhuang X, Xiang X, Grizzle W, et al. Treatment of brain inflammatory diseases by delivering exosome encapsulated anti-inflammatory drugs from the nasal region to the brain. Mol Ther 2011; 19(10): 1769-79.
[156]
Cooper JM, Wiklander PB, Nordin JZ, et al. Systemic exosomal siRNA delivery reduced alpha-synuclein aggregates in brains of transgenic mice. Mov Disord 2014; 29(12): 1476-85.
[157]
Liu Y, Li D, Liu Z, et al. Targeted exosome-mediated delivery of opioid receptor Mu siRNA for the treatment of morphine relapse. Sci Rep 2015; 5: 17543.
[158]
Jang SC, Kim OY, Yoon CM, et al. Bioinspired exosome-mimetic nanovesicles for targeted delivery of chemotherapeutics to malignant tumors. ACS Nano 2013; 7(9): 7698-710.
[159]
Yoon J, Jo W, Jeong D, Kim J, Jeong H, Park J. Generation of nanovesicles with sliced cellular membrane fragments for exogenous material delivery. Biomaterials 2015; 59: 12-20.
[160]
De La Peña H, Madrigal JA, Rusakiewicz S, et al. Artificial exosomes as tools for basic and clinical immunology. J Immunol Methods 2009; 344(2): 121-32.
[161]
Brunner J, Skrabal P, Hauser H. Single bilayer vesicles prepared without sonication. Physico-chemical properties. Biochim Biophys Acta 1976; 455(2): 322-31.
[162]
Bangham AD, Standish MM, Watkins JC. Diffusion of univalent ions across the lamellae of swollen phospholipids. J Mol Biol 1965; 13(1): 238-52.
[163]
Woodbury DJ, Richardson ES, Grigg AW, Welling RD, Knudson BH. Reducing liposome size with ultrasound: Bimodal size distributions. J Liposome Res 2006; 16(1): 57-80.
[164]
Jousma H, Talsma H, Spies F, Joosten JGH, Junginger HE, Crommelin DJA. Characterization of liposomes the influence of extrusion of multilamellar vesicles through polycarbonate membranes on particle size particle size distribution and number of bilayers. Int J Pharm 1987; 35(3): 263-74.
[165]
Meure LA, Foster NR, Dehghani F. Conventional and dense gas techniques for the production of liposomes: A review. AAPS PharmSciTech 2008; 9(3): 798-809.
[166]
Frederiksen L, Anton K, van Hoogevest P, Keller HR, Leuenberger H. Preparation of liposomes encapsulating water-soluble compounds using supercritical carbon dioxide. J Pharm Sci 1997; 86(8): 921-8.
[167]
Aburai K, Yagi N, Yokoyama Y, et al. Preparation of liposomes modified with lipopeptides using a supercritical carbon dioxide reverse-phase evaporation method. J Oleo Sci 2011; 60(5): 209-15.
[168]
Cano-Sarabia M, Ventosa N, Sala S, Patiño C, Arranz R, Veciana J. Preparation of uniform rich cholesterol unilamellar nanovesicles using CO2-expanded solvents. Langmuir 2008; 24(6): 2433-7.
[169]
Jahn A, Vreeland WN, Gaitan M, Locascio LE. Controlled vesicle self-assembly in microfluidic channels with hydrodynamic focusing. J Am Chem Soc 2004; 126(9): 2674-5.
[170]
Balbino TA, Azzoni AR, de la Torre LG. Microfluidic devices for continuous production of pDNA/cationic liposome complexes for gene delivery and vaccine therapy. Colloids Surf B Biointerfaces 2013; 111: 203-10.
[171]
Wang T, Deng Y, Geng Y, Gao Z, Zou J, Wang Z. Preparation of submicron unilamellar liposomes by freeze-drying double emulsions. Biochim Biophys Acta 2006; 1758(2): 222-31.
[172]
Jaafar-Maalej C, Charcosset C, Fessi H. A new method for liposome preparation using a membrane contactor. J Liposome Res 2011; 21(3): 213-20.
[173]
Laouini A, Jaafar-Maalej C, Sfar S, Charcosset C, Fessi H. Liposome preparation using a hollow fiber membrane contactor--application to spironolactone encapsulation. Int J Pharm 2011; 415(1-2): 53-61.
[174]
Mokhtarieh AA, Cheong S, Kim S, Chung BH, Lee MK. Asymmetric liposome particles with highly efficient encapsulation of siRNA and without nonspecific cell penetration suitable for target-specific delivery. Biochim Biophys Acta Biomembr 2012; 1818: 1633-41.
[175]
Vardhanabhuti N, Ramachandran C, Schacht J, Weiner N. Preparation of liposomes with asymmetric distribution of phosphyatidylinositol 4,5- bisphosphate across the bilayer. J Liposome Res 1997; 7: 301-14.
[176]
Denkins YM, Schroit AJ. Phosphatidylserine decarboxylase: generation of asymmetric vesicles and determination of the transbilayer distribution of fluorescent phosphatidylserine in model membrane systems. Biochim Biophys Acta Biomembr 1986; 862: 343-51.
[177]
Whittenton J, Harendra S, Pitchumani R, Mohanty K, Vipulanandan C, Thevananther S. Evaluation of asymmetric liposomal nanoparticles for encapsulation of polynucleotides. Langmuir 2008; 24(16): 8533-40.
[178]
Ceh B, Lasic DD. A rigorous theory of remote loading of drugs into liposomes. Langmuir 1995; 11(9): 3356-68.
[179]
Gajos K, Kamińska A, Awsiuk K, et al. Immobilization and detection of platelet-derived extracellular vesicles on functionalized silicon substrate: cytometric and spectrometric approach. Anal Bioanal Chem 2017; 409(4): 1109-19.
[180]
Record M, Carayon K, Poirot M, Silvente-Poirot S. Exosomes as new vesicular lipid transporters involved in cell-cell communication and various pathophysiologies. Biochim Biophys Acta 2014; 1841(1): 108-20.
[181]
Xiang X, Poliakov A, Liu C, et al. Induction of myeloid-derived suppressor cells by tumor exosomes. Int J Cancer 2009; 124(11): 2621-33.
[182]
Llorente A, Skotland T, Sylvänne T, et al. Molecular lipidomics of exosomes released by PC-3 prostate cancer cells. Biochim Biophys Acta 2013; 1831(7): 1302-9.
[183]
Phuyal S, Skotland T, Hessvik NP, et al. The ether lipid precursor hexadecylglycerol stimulates the release and changes the composition of exosomes derived from PC-3 cells. J Biol Chem 2015; 290(7): 4225-37.
[184]
Wubbolts R, Leckie RS, Veenhuizen PT, et al. Proteomic and biochemical analyses of human B cell-derived exosomes. Potential implications for their function and multivesicular body formation. J Biol Chem 2003; 278(13): 10963-72.
[185]
Laulagnier K, Motta C, Hamdi S, et al. Mast cell- and dendritic cell-derived exosomes display a specific lipid composition and an unusual membrane organization. Biochem J 2004; 380(Pt 1): 161-71.
[186]
Vidal M, Sainte-Marie J, Philippot JR, Bienvenue A. Asymmetric distribution of phospholipids in the membrane of vesicles released during in vitro maturation of guinea pig reticulocytes: evidence precluding a role for “aminophospholipid translocase”. J Cell Physiol 1989; 140(3): 455-62.
[187]
Brouwers JF, Aalberts M, Jansen JW, et al. Distinct lipid compositions of two types of human prostasomes. Proteomics 2013; 13(10-11): 1660-6.
[188]
Skotland T, Ekroos K, Kauhanen D, et al. Molecular lipid species in urinary exosomes as potential prostate cancer biomarkers. Eur J Cancer 2017; 70: 122-32.
[189]
Pienimaeki-Roemer A, Kuhlmann K, Böttcher A, et al. Lipidomic and proteomic characterization of platelet extracellular vesicle subfractions from senescent platelets. Transfusion 2015; 55(3): 507-21.
[190]
Ercole F, Whittaker MR, Quinn JF, Davis TP. Cholesterol modified self-assemblies and their application to nanomedicine. Biomacromolecules 2015; 16(7): 1886-914.
[191]
Moghimi SM, Patel HM. Serum opsonins and phagocytosis of saturated and unsaturated phospholipid liposomes. Biochim Biophys Acta 1989; 984(3): 384-7.
[192]
Allen TM, Chonn A. Large unilamellar liposomes with low uptake into the reticuloendothelial system. FEBS Lett 1987; 223(1): 42-6.
[193]
Webb MS, Harasym TO, Masin D, Bally MB, Mayer LD. Sphingomyelin-cholesterol liposomes significantly enhance the pharmacokinetic and therapeutic properties of vincristine in murine and human tumour models. Br J Cancer 1995; 72(4): 896-904.
[194]
Senior J, Gregoriadis G. Is half-life of circulating liposomes determined by changes in their permeability? FEBS Lett 1982; 145(1): 109-14.
[195]
Johnstone SA, Masin D, Mayer L, Bally MB. Surface-associated serum proteins inhibit the uptake of phosphatidylserine and poly(ethylene glycol) liposomes by mouse macrophages. Biochim Biophys Acta 2001; 1513(1): 25-37.
[196]
Allen TM, Hansen C, Martin F, Redemann C, Yau-Young A. Liposomes containing synthetic lipid derivatives of poly(ethylene glycol) show prolonged circulation half-lives in vivo. Biochim Biophys Acta 1991; 1066(1): 29-36.
[197]
Nazarenko I, Rana S, Baumann A, et al. Cell surface tetraspanin Tspan8 contributes to molecular pathways of exosome-induced endothelial cell activation. Cancer Res 2010; 70(4): 1668-78.
[198]
Potolicchio I, Carven GJ, Xu X, et al. Proteomic analysis of microglia-derived exosomes: metabolic role of the aminopeptidase CD13 in neuropeptide catabolism. J Immunol 2005; 175(4): 2237-43.
[199]
Luga V, Zhang L, Viloria-Petit AM, et al. Exosomes mediate stromal mobilization of autocrine Wnt-PCP signaling in breast cancer cell migration. Cell 2012; 151(7): 1542-56.
[200]
Admyre C, Johansson SM, Qazi KR, et al. Exosomes with immune modulatory features are present in human breast milk. J Immunol 2007; 179(3): 1969-78.
[201]
Iavello A, Frech VS, Gai C, Deregibus MC, Quesenberry PJ, Camussi G. Role of Alix in miRNA packaging during extracellular vesicle biogenesis. Int J Mol Med 2016; 37(4): 958-66.
[202]
Carayon K, Chaoui K, Ronzier E, et al. Proteolipidic composition of exosomes changes during reticulocyte maturation. J Biol Chem 2011; 286(39): 34426-39.
[203]
Perez-Pujol S, Marker PH, Key NS. Platelet microparticles are heterogeneous and highly dependent on the activation mechanism: studies using a new digital flow cytometer. Cytometry A 2007; 71(1): 38-45.
[204]
Mobarrez F, Abraham-Nordling M, Aguilera-Gatica K, et al. The expression of microvesicles in the blood of patients with Graves’ disease and its relationship to treatment. Clin Endocrinol (Oxf) 2016; 84(5): 729-35.
[205]
Laghezza Masci V, Taddei AR, Gambellini G, Giorgi F, Fausto AM. Microvesicles shed from fibroblasts act as metalloproteinase carriers in a 3-D collagen matrix. J Circ Biomark 2016; 51849454416663660
[206]
Haraszti RA, Didiot MC, Sapp E, et al. High-resolution proteomic and lipidomic analysis of exosomes and microvesicles from different cell sources. J Extracell Vesicles 2016; 5: 32570.
[207]
Ashley J, Cordy B, Lucia D, Fradkin LG, Budnik V, Thomson T. Retrovirus-like Gag protein Arc1 binds RNA and traffics across synaptic boutons. Cell 2018; 172(1-2): 262-274.e11.
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