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PMID: 22619510 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Review

Exosome mimetics: a novel class of drug delivery systems.

International journal of nanomedicine ·Vol. 7 ·2012-00-00 ·Pages 1525-41

Kooijmans SA, Vader P, van Dommelen SM, van Solinge WW, Schiffelers RM

Abstract

The identification of extracellular phospholipid vesicles as conveyors of cellular information has created excitement in the field of drug delivery. Biological therapeutics, including short interfering RNA and recombinant proteins, are prone to degradation, have limited ability to cross biological membranes, and may elicit immune responses. Therefore, delivery systems for such drugs are under intensive investigation. Exploiting extracellular vesicles as carriers for biological therapeutics is a promising strategy to overcome these issues and to achieve efficient delivery to the cytosol of target cells. Exosomes are a well studied class of extracellular vesicles known to carry proteins and nucleic acids, making them especially suitable for such strategies. However, the considerable complexity and the related high chance of off-target effects of these carriers are major barriers for translation to the clinic. Given that it is well possible that not all components of exosomes are required for their proper functioning, an alternative strategy would be to mimic these vesicles synthetically. By assembly of liposomes harboring only crucial components of natural exosomes, functional exosome mimetics may be created. The low complexity and use of well characterized components strongly increase the pharmaceutical acceptability of such systems. However, exosomal components that would be required for the assembly of functional exosome mimetics remain to be identified. This review provides insights into the composition and functional properties of exosomes, and focuses on components which could be used to enhance the drug delivery properties of exosome mimetics.

Keywords
drug delivery systems exosomes extracellular vesicles liposomes
MeSH Terms
Animals Biomimetic Materials/chemistry Biotechnology Cell Adhesion Molecules/chemistry Drug Carriers/chemistry Drug Delivery Systems Exosomes/chemistry Humans Liposomes/chemistry Membrane Lipids/chemistry Membrane Proteins/chemistry Nanomedicine Nanotechnology RNA, Small Interfering/administration & dosage Tetraspanins/chemistry
Chemicals
Cell Adhesion Molecules Drug Carriers Liposomes Membrane Lipids Membrane Proteins RNA, Small Interfering Tetraspanins
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Kooijmans Sander A A
Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, The Netherlands.
Vader Pieter
van Dommelen Susan M
van Solinge Wouter W
Schiffelers Raymond M
References (196)
196 references, click to expand
  1. Functional reconstitution of a voltage-gated potassium channel in giant unilamellar vesicles.
    PLoS One. 2011;6(10):e25529 PMID: 21998666
  2. Mechanism of transfer of functional microRNAs between mouse dendritic cells via exosomes.
    Blood. 2012 Jan 19;119(3):756-66 PMID: 22031862
  3. Vincristine sulfate liposomes injection (Marqibo) in heavily pretreated patients with refractory aggressive non-Hodgkin lymphoma: report of the pivotal phase 2 study.
    Cancer. 2009 Aug 1;115(15):3475-82 PMID: 19536896
  4. MicroRNA replacement therapy for cancer.
    Pharm Res. 2011 Dec;28(12):3030-42 PMID: 21879389
  5. Lactadherin binds to phosphatidylserine-containing vesicles in a two-step mechanism sensitive to vesicle size and composition.
    Biochim Biophys Acta. 2012 Apr;1818(4):1019-27 PMID: 21920348
  6. Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers.
    Nat Cell Biol. 2008 Dec;10(12):1470-6 PMID: 19011622
  7. Proteomic and biochemical analyses of human B cell-derived exosomes. Potential implications for their function and multivesicular body formation.
    J Biol Chem. 2003 Mar 28;278(13):10963-72 PMID: 12519789
  8. The microRNA miR-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44.
    Nat Med. 2011 Feb;17(2):211-5 PMID: 21240262
  9. Emission of membrane vesicles: roles in complement resistance, immunity and cancer.
    Springer Semin Immunopathol. 2005 Nov;27(3):375-87 PMID: 16189651
  10. miR-22 represses cancer progression by inducing cellular senescence.
    J Cell Biol. 2011 Apr 18;193(2):409-24 PMID: 21502362
  11. Molecular mechanisms of calcium-induced membrane fusion.
    J Bioenerg Biomembr. 1990 Apr;22(2):157-79 PMID: 2139437
  12. Thrombospondins in cancer.
    Cell Mol Life Sci. 2008 Mar;65(5):700-12 PMID: 18193162
  13. Strategies for the cell-free expression of membrane proteins.
    Methods Mol Biol. 2010;607:187-212 PMID: 20204858
  14. ICAM-1 on exosomes from mature dendritic cells is critical for efficient naive T-cell priming.
    Blood. 2005 Jul 1;106(1):216-23 PMID: 15790784
  15. Diacylglycerol kinase α regulates the formation and polarisation of mature multivesicular bodies involved in the secretion of Fas ligand-containing exosomes in T lymphocytes.
    Cell Death Differ. 2011 Jul;18(7):1161-73 PMID: 21252909
  16. Phosphatidylserine-containing liposomes: potential pharmacological interventions against inflammatory and immune diseases through the production of prostaglandin E(2) after uptake by myeloid derived phagocytes.
    Arch Immunol Ther Exp (Warsz). 2011 Jun;59(3):195-201 PMID: 21479802
  17. Requirement of CD9 on the egg plasma membrane for fertilization.
    Science. 2000 Jan 14;287(5451):321-4 PMID: 10634791
  18. The promises and pitfalls of RNA-interference-based therapeutics.
    Nature. 2009 Jan 22;457(7228):426-33 PMID: 19158789
  19. Promotion of vesicular stomatitis virus fusion by the endosome-specific phospholipid bis(monoacylglycero)phosphate (BMP).
    FEBS Lett. 2011 Mar 23;585(6):865-9 PMID: 21333650
  20. Inhibition of liposome-induced complement activation by incorporated poly(ethylene glycol)-lipids.
    Arch Biochem Biophys. 1998 Sep 15;357(2):185-94 PMID: 9735159
  21. Visualizing of the cellular uptake and intracellular trafficking of exosomes by live-cell microscopy.
    J Cell Biochem. 2010 Oct 1;111(2):488-96 PMID: 20533300
  22. Proteomics analysis of bladder cancer exosomes.
    Mol Cell Proteomics. 2010 Jun;9(6):1324-38 PMID: 20224111
  23. CD63 tetraspanin slows down cell migration and translocates to the endosomal-lysosomal-MIICs route after extracellular stimuli in human immature dendritic cells.
    Blood. 2004 Aug 15;104(4):1183-90 PMID: 15130945
  24. EGF stimulates annexin 1-dependent inward vesiculation in a multivesicular endosome subpopulation.
    EMBO J. 2006 Jan 11;25(1):1-12 PMID: 16052208
  25. Membrane microparticles: two sides of the coin.
    Physiology (Bethesda). 2005 Feb;20:22-7 PMID: 15653836
  26. Cells release prions in association with exosomes.
    Proc Natl Acad Sci U S A. 2004 Jun 29;101(26):9683-8 PMID: 15210972
  27. Vaccination of metastatic melanoma patients with autologous dendritic cell (DC) derived-exosomes: results of thefirst phase I clinical trial.
    J Transl Med. 2005 Mar 02;3(1):10 PMID: 15740633
  28. Endothelial expression of autocrine VEGF upon the uptake of tumor-derived microvesicles containing oncogenic EGFR.
    Proc Natl Acad Sci U S A. 2009 Mar 10;106(10):3794-9 PMID: 19234131
  29. The human P2X7 receptor and its role in innate immunity.
    Tissue Antigens. 2011 Nov;78(5):321-32 PMID: 21988719
  30. A phase I study of dexosome immunotherapy in patients with advanced non-small cell lung cancer.
    J Transl Med. 2005 Feb 21;3(1):9 PMID: 15723705
  31. Direct observation of ligand binding to membrane proteins in living cells by a saturation transfer double difference (STDD) NMR spectroscopy method shows a significantly higher affinity of integrin alpha(IIb)beta3 in native platelets than in liposomes.
    J Am Chem Soc. 2005 Jan 26;127(3):916-9 PMID: 15656629
  32. Role of transmembrane 4 superfamily (TM4SF) proteins CD9 and CD81 in muscle cell fusion and myotube maintenance.
    J Cell Biol. 1999 Aug 23;146(4):893-904 PMID: 10459022
  33. CD8+ dendritic cells use LFA-1 to capture MHC-peptide complexes from exosomes in vivo.
    J Immunol. 2007 Aug 1;179(3):1489-96 PMID: 17641014
  34. Apoptotic bodies from endothelial cells enhance the number and initiate the differentiation of human endothelial progenitor cells in vitro.
    Blood. 2004 Nov 1;104(9):2761-6 PMID: 15242875
  35. ExoCarta 2012: database of exosomal proteins, RNA and lipids.
    Nucleic Acids Res. 2012 Jan;40(Database issue):D1241-4 PMID: 21989406
  36. Microenvironmental influences of apoptosis in vivo and in vitro.
    Apoptosis. 2010 Sep;15(9):1029-49 PMID: 20237956
  37. Protein targeting to exosomes/microvesicles by plasma membrane anchors.
    J Biol Chem. 2011 Apr 22;286(16):14383-95 PMID: 21300796
  38. Effect of increased extracellular ca on microvesicle production and tumor spheroid formation.
    Cancer Microenviron. 2010 Jul 13;4(1):93-103 PMID: 21505564
  39. Large unilamellar liposomes with low uptake into the reticuloendothelial system.
    FEBS Lett. 1987 Oct 19;223(1):42-6 PMID: 3666140
  40. The C-terminal tail of tetraspanin protein CD9 contributes to its function and molecular organization.
    J Cell Sci. 2011 Aug 15;124(Pt 16):2702-10 PMID: 21771881
  41. Endocytosis, intracellular sorting, and processing of exosomes by dendritic cells.
    Blood. 2004 Nov 15;104(10):3257-66 PMID: 15284116
  42. Characterization of exosome-like vesicles released from human tracheobronchial ciliated epithelium: a possible role in innate defense.
    FASEB J. 2009 Jun;23(6):1858-68 PMID: 19190083
  43. Targeting tumor antigens to secreted membrane vesicles in vivo induces efficient antitumor immune responses.
    Cancer Res. 2008 Feb 15;68(4):1228-35 PMID: 18281500
  44. Tetraspanins: push and pull in suppressing and promoting metastasis.
    Nat Rev Cancer. 2009 Jan;9(1):40-55 PMID: 19078974
  45. Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma.
    Proc Natl Acad Sci U S A. 2011 Mar 22;108(12):5003-8 PMID: 21383194
  46. Characterization of bovine serum factor triggering the lysis of liposomes via complement activation.
    Biol Pharm Bull. 1998 Apr;21(4):390-7 PMID: 9586579
  47. Monocyte-derived microparticles and exosomes induce procoagulant and apoptotic effects on endothelial cells.
    Thromb Haemost. 2008 Nov;100(5):878-85 PMID: 18989533
  48. Tetraspanin functions and associated microdomains.
    Nat Rev Mol Cell Biol. 2005 Oct;6(10):801-11 PMID: 16314869
  49. ExoCarta: A compendium of exosomal proteins and RNA.
    Proteomics. 2009 Nov;9(21):4997-5000 PMID: 19810033
  50. Cancer therapy via modulation of micro RNA levels: a promising future.
    Drug Discov Today. 2010 Sep;15(17-18):733-40 PMID: 20692360
  51. The nature and significance of platelet products in human plasma.
    Br J Haematol. 1967 May;13(3):269-88 PMID: 6025241
  52. Calcium induces phospholipid redistribution and microvesicle release in human erythrocyte membranes by independent pathways.
    Biochemistry. 1998 Nov 3;37(44):15383-91 PMID: 9799499
  53. Exosomes from ovarian cancer cells induce adipose tissue-derived mesenchymal stem cells to acquire the physical and functional characteristics of tumor-supporting myofibroblasts.
    Gynecol Oncol. 2011 Nov;123(2):379-86 PMID: 21903249
  54. Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes.
    Nat Biotechnol. 2011 Apr;29(4):341-5 PMID: 21423189
  55. Increasing vaccine potency through exosome antigen targeting.
    Vaccine. 2011 Nov 21;29(50):9361-7 PMID: 22001882
  56. Microenvironmental pH is a key factor for exosome traffic in tumor cells.
    J Biol Chem. 2009 Dec 4;284(49):34211-22 PMID: 19801663
  57. Cell-free synthesis of functional aquaporin Z in synthetic liposomes.
    Biotechnol Bioeng. 2009 Sep 1;104(1):40-9 PMID: 19557835
  58. Polymers in small-interfering RNA delivery.
    Nucleic Acid Ther. 2011 Jun;21(3):133-47 PMID: 21749290
  59. Lipid-based nanoparticles as pharmaceutical drug carriers: from concepts to clinic.
    Crit Rev Ther Drug Carrier Syst. 2009;26(6):523-80 PMID: 20402623
  60. Liposomes and nanoparticles: nanosized vehicles for drug delivery in cancer.
    Trends Pharmacol Sci. 2009 Nov;30(11):592-9 PMID: 19837467
  61. Exosomes from human CD34(+) stem cells mediate their proangiogenic paracrine activity.
    Circ Res. 2011 Sep 16;109(7):724-8 PMID: 21835908
  62. Tissue-factor-bearing microvesicles arise from lipid rafts and fuse with activated platelets to initiate coagulation.
    Blood. 2005 Sep 1;106(5):1604-11 PMID: 15741221
  63. Sphingomyelin/cholesterol liposomal vincristine: a new formulation for an old drug.
    Expert Opin Biol Ther. 2006 Apr;6(4):409-15 PMID: 16548767
  64. Regulatory role of GM3 ganglioside in alpha 5 beta 1 integrin receptor for fibronectin-mediated adhesion of FUA169 cells.
    J Biol Chem. 1993 Jan 25;268(3):2217-22 PMID: 8420989
  65. Exosome nanotechnology: an emerging paradigm shift in drug delivery: exploitation of exosome nanovesicles for systemic in vivo delivery of RNAi heralds new horizons for drug delivery across biological barriers.
    Bioessays. 2011 Oct;33(10):737-41 PMID: 21932222
  66. Proteomic analysis of microvesicles derived from human colorectal cancer cells.
    J Proteome Res. 2007 Dec;6(12):4646-55 PMID: 17956143
  67. Integrins.
    Cell Tissue Res. 2010 Jan;339(1):269-80 PMID: 19693543
  68. Tetraspanins in viral infections: a fundamental role in viral biology?
    J Virol. 2005 Sep;79(17):10839-51 PMID: 16103137
  69. Exosomes as intercellular signalosomes and pharmacological effectors.
    Biochem Pharmacol. 2011 May 15;81(10):1171-82 PMID: 21371441
  70. Engineering RNA for targeted siRNA delivery and medical application.
    Adv Drug Deliv Rev. 2010 Apr 30;62(6):650-66 PMID: 20230868
  71. Efficient siRNA delivery with non-viral polymeric vehicles.
    Pharm Res. 2009 Mar;26(3):657-66 PMID: 19015957
  72. miR-21-mediated tumor growth.
    Oncogene. 2007 Apr 26;26(19):2799-803 PMID: 17072344
  73. Monocyte derived microvesicles deliver a cell death message via encapsulated caspase-1.
    PLoS One. 2009 Sep 25;4(9):e7140 PMID: 19779610
  74. Exosomes account for vesicle-mediated transcellular transport of activatable phospholipases and prostaglandins.
    J Lipid Res. 2010 Aug;51(8):2105-20 PMID: 20424270
  75. "Smart" liposomal nanocontainers in biology and medicine.
    Biochemistry (Mosc). 2010 Jul;75(7):811-24 PMID: 20673204
  76. B-Raf(V600E) and thrombospondin-1 promote thyroid cancer progression.
    Proc Natl Acad Sci U S A. 2010 Jun 8;107(23):10649-54 PMID: 20498063
  77. Protein-lipid interplay in fusion and fission of biological membranes.
    Annu Rev Biochem. 2003;72:175-207 PMID: 14527322
  78. Molecular biology. The art of assembly.
    Science. 2008 Feb 1;319(5863):578-9 PMID: 18239114
  79. SiRNA delivery with exosome nanoparticles.
    Nat Biotechnol. 2011 Apr;29(4):325-6 PMID: 21478846
  80. Human plasma membrane-derived vesicles inhibit the phagocytosis of apoptotic cells--possible role in SLE.
    Biochem Biophys Res Commun. 2010 Jul 23;398(2):278-83 PMID: 20599722
  81. An E2F/miR-20a autoregulatory feedback loop.
    J Biol Chem. 2007 Jan 26;282(4):2135-43 PMID: 17135249
  82. Mast cell- and dendritic cell-derived exosomes display a specific lipid composition and an unusual membrane organization.
    Biochem J. 2004 May 15;380(Pt 1):161-71 PMID: 14965343
  83. Exosome lipidomics unravels lipid sorting at the level of multivesicular bodies.
    Biochimie. 2007 Feb;89(2):205-12 PMID: 17157973
  84. Apoptosis induction by antisense oligonucleotides against miR-17-5p and miR-20a in lung cancers overexpressing miR-17-92.
    Oncogene. 2007 Sep 6;26(41):6099-105 PMID: 17384677
  85. Liposomal nanomedicines.
    Expert Opin Drug Deliv. 2008 Jan;5(1):25-44 PMID: 18095927
  86. Microparticles, thrombosis and cancer.
    Best Pract Res Clin Haematol. 2009 Mar;22(1):61-9 PMID: 19285273
  87. Cellular mechanisms underlying the formation of circulating microparticles.
    Arterioscler Thromb Vasc Biol. 2011 Jan;31(1):15-26 PMID: 21160064
  88. Elastic deformation and failure of lipid bilayer membranes containing cholesterol.
    Biophys J. 1990 Oct;58(4):997-1009 PMID: 2249000
  89. Thrombospondin-based antiangiogenic therapy.
    Microvasc Res. 2007 Sep-Nov;74(2-3):90-9 PMID: 17559888
  90. Interactions of Triton X-100 with sphingomyelin and phosphatidylcholine monolayers: influence of the cholesterol content.
    Colloids Surf B Biointerfaces. 2008 Oct 15;66(2):163-7 PMID: 18644701
  91. Exosome/microvesicle-mediated epigenetic reprogramming of cells.
    Am J Cancer Res. 2011;1(1):98-110 PMID: 21969178
  92. Microparticles in angiogenesis: therapeutic potential.
    Circ Res. 2011 Jun 24;109(1):110-9 PMID: 21700952
  93. Strategies for silencing human disease using RNA interference.
    Nat Rev Genet. 2007 Mar;8(3):173-84 PMID: 17304245
  94. Microvesicles and viral infection.
    J Virol. 2011 Dec;85(24):12844-54 PMID: 21976651
  95. Inhibition of cancer stem cell-like properties and reduced chemoradioresistance of glioblastoma using microRNA145 with cationic polyurethane-short branch PEI.
    Biomaterials. 2012 Feb;33(5):1462-76 PMID: 22098779
  96. A novel strategy to modify adenovirus tropism and enhance transgene delivery to activated vascular endothelial cells in vitro and in vivo.
    Hum Gene Ther. 2004 May;15(5):433-43 PMID: 15144574
  97. C-type lectin DC-SIGN: an adhesion, signalling and antigen-uptake molecule that guides dendritic cells in immunity.
    Cell Signal. 2010 Oct;22(10):1397-405 PMID: 20363321
  98. Platelet-derived microparticles stimulate proliferation, survival, adhesion, and chemotaxis of hematopoietic cells.
    Exp Hematol. 2002 May;30(5):450-9 PMID: 12031651
  99. Integrin alphaIIb beta3 reconstituted into lipid bilayers is nonclustered in its activated state but clusters after fibrinogen binding.
    Biochemistry. 1997 Jun 17;36(24):7395-402 PMID: 9200686
  100. Identification of a functional role for lipid asymmetry in biological membranes: Phosphatidylserine-skeletal protein interactions modulate membrane stability.
    Proc Natl Acad Sci U S A. 2002 Feb 19;99(4):1943-8 PMID: 11830646
  101. The presence of contractile proteins in platelet microparticles isolated from human and animal platelet-free plasma.
    Br J Haematol. 1971 Jul;21(1):53-69 PMID: 4254312
  102. Apoptosis, subcellular particles, and autoimmunity.
    Clin Immunol. 2004 Aug;112(2):175-82 PMID: 15240161
  103. Tetraspanins CD9 and CD81 function to prevent the fusion of mononuclear phagocytes.
    J Cell Biol. 2003 Jun 9;161(5):945-56 PMID: 12796480
  104. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells.
    Nat Cell Biol. 2007 Jun;9(6):654-9 PMID: 17486113
  105. Advances in membranous vesicle and exosome proteomics improving biological understanding and biomarker discovery.
    Proteomics. 2011 Feb;11(4):709-20 PMID: 21241021
  106. Functional delivery of viral miRNAs via exosomes.
    Proc Natl Acad Sci U S A. 2010 Apr 6;107(14):6328-33 PMID: 20304794
  107. Enabling a robust scalable manufacturing process for therapeutic exosomes through oncogenic immortalization of human ESC-derived MSCs.
    J Transl Med. 2011 Apr 25;9:47 PMID: 21513579
  108. A novel nanoparticle drug delivery system: the anti-inflammatory activity of curcumin is enhanced when encapsulated in exosomes.
    Mol Ther. 2010 Sep;18(9):1606-14 PMID: 20571541
  109. Assessing the nature of lipid raft membranes.
    PLoS Comput Biol. 2007 Feb 23;3(2):e34 PMID: 17319738
  110. Ca(++)-dependent vesicle release from erythrocytes involves stomatin-specific lipid rafts, synexin (annexin VII), and sorcin.
    Blood. 2002 Apr 1;99(7):2569-77 PMID: 11895795
  111. A simple method for the reconstitution of membrane proteins into giant unilamellar vesicles.
    J Membr Biol. 2010 Feb;233(1-3):85-92 PMID: 20135103
  112. Morphologic and proteomic characterization of exosomes released by cultured extravillous trophoblast cells.
    Exp Cell Res. 2011 May 1;317(8):1192-202 PMID: 21276792
  113. Cell-free expression as an emerging technique for the large scale production of integral membrane protein.
    FEBS J. 2006 Sep;273(18):4141-53 PMID: 16930130
  114. Integrin structure, activation, and interactions.
    Cold Spring Harb Perspect Biol. 2011 Mar 01;3(3): PMID: 21421922
  115. Treatment of brain inflammatory diseases by delivering exosome encapsulated anti-inflammatory drugs from the nasal region to the brain.
    Mol Ther. 2011 Oct;19(10):1769-79 PMID: 21915101
  116. Aberrant miR-182 expression promotes melanoma metastasis by repressing FOXO3 and microphthalmia-associated transcription factor.
    Proc Natl Acad Sci U S A. 2009 Feb 10;106(6):1814-9 PMID: 19188590
  117. Optimizing liposomes for delivery of chemotherapeutic agents to solid tumors.
    Pharmacol Rev. 1999 Dec;51(4):691-743 PMID: 10581328
  118. Proteomic analysis of microglia-derived exosomes: metabolic role of the aminopeptidase CD13 in neuropeptide catabolism.
    J Immunol. 2005 Aug 15;175(4):2237-43 PMID: 16081791
  119. Autoantigens are translocated into small apoptotic bodies during early stages of apoptosis.
    Cell Death Differ. 2008 Jan;15(1):183-91 PMID: 17932498
  120. Endothelial microparticle formation in moderate concentrations of homocysteine and methionine in vitro.
    Cell Mol Biol Lett. 2011 Mar;16(1):69-78 PMID: 21161416
  121. Exosome Display technology: applications to the development of new diagnostics and therapeutics.
    Blood Cells Mol Dis. 2005 Sep-Oct;35(2):158-68 PMID: 16087368
  122. Cooperation between decay-accelerating factor and membrane cofactor protein in protecting cells from autologous complement attack.
    J Immunol. 2000 Oct 1;165(7):3999-4006 PMID: 11034410
  123. Phosphatidylserine as a determinant of reticuloendothelial recognition of liposome models of the erythrocyte surface.
    Proc Natl Acad Sci U S A. 1988 Nov;85(21):8067-71 PMID: 3186707
  124. Dengue virus ensures its fusion in late endosomes using compartment-specific lipids.
    PLoS Pathog. 2010 Oct 07;6(10):e1001131 PMID: 20949067
  125. Characterisation of exosomes derived from human cells by nanoparticle tracking analysis and scanning electron microscopy.
    Colloids Surf B Biointerfaces. 2011 Oct 1;87(1):146-50 PMID: 21640565
  126. RGD-based strategies for selective delivery of therapeutics and imaging agents to the tumour vasculature.
    Drug Resist Updat. 2005 Dec;8(6):381-402 PMID: 16309948
  127. Endocytic recycling.
    Nat Rev Mol Cell Biol. 2004 Feb;5(2):121-32 PMID: 15040445
  128. Targeting of tetraspanin proteins--potential benefits and strategies.
    Nat Rev Drug Discov. 2008 Sep;7(9):747-58 PMID: 18758472
  129. Crystal structure of the bovine lactadherin C2 domain, a membrane binding motif, shows similarity to the C2 domains of factor V and factor VIII.
    J Mol Biol. 2007 Aug 17;371(3):717-24 PMID: 17583728
  130. Microvesicles: mediators of extracellular communication during cancer progression.
    J Cell Sci. 2010 May 15;123(Pt 10):1603-11 PMID: 20445011
  131. Exovesicles from human activated dendritic cells fuse with resting dendritic cells, allowing them to present alloantigens.
    Am J Pathol. 2006 Dec;169(6):2127-36 PMID: 17148675
  132. Angiogenic endothelium shows lactadherin-dependent phagocytosis of aged erythrocytes and apoptotic cells.
    Blood. 2008 May 1;111(9):4542-50 PMID: 18292292
  133. Morphological assessment of apoptosis.
    Methods. 2008 Mar;44(3):200-4 PMID: 18314050
  134. MHC class II-associated proteins in B-cell exosomes and potential functional implications for exosome biogenesis.
    Immunol Cell Biol. 2010 Nov-Dec;88(8):851-6 PMID: 20458337
  135. Thrombospondin-1 (TSP-1) Stimulates Expression of Integrin alpha6 in Human Breast Carcinoma Cells: A Downstream Modulator of TSP-1-Induced Cellular Adhesion.
    J Oncol. 2010;2010:645376 PMID: 20631908
  136. The complement-inhibitory activity of CD59 resides in its capacity to block incorporation of C9 into membrane C5b-9.
    J Immunol. 1990 May 1;144(9):3478-83 PMID: 1691760
  137. C2C12 myoblasts release micro-vesicles containing mtDNA and proteins involved in signal transduction.
    Exp Cell Res. 2010 Jul 15;316(12):1977-84 PMID: 20399774
  138. Direct formation of proteo-liposomes by in vitro synthesis and cellular cytosolic delivery with connexin-expressing liposomes.
    Biomaterials. 2009 Aug;30(23-24):3971-7 PMID: 19423159
  139. Difference gel electrophoresis analysis of Ras-transformed fibroblast cell-derived exosomes.
    Electrophoresis. 2008 Jun;29(12):2660-71 PMID: 18494037
  140. Selective enrichment of tetraspan proteins on the internal vesicles of multivesicular endosomes and on exosomes secreted by human B-lymphocytes.
    J Biol Chem. 1998 Aug 7;273(32):20121-7 PMID: 9685355
  141. The influence of membrane physical properties on microvesicle release in human erythrocytes.
    PMC Biophys. 2009 Aug 24;2(1):7 PMID: 19703298
  142. Large-scale proteomics and phosphoproteomics of urinary exosomes.
    J Am Soc Nephrol. 2009 Feb;20(2):363-79 PMID: 19056867
  143. Proteomic analysis of human parotid gland exosomes by multidimensional protein identification technology (MudPIT).
    J Proteome Res. 2009 Mar;8(3):1304-14 PMID: 19199708
  144. Membrane vesicles as conveyors of immune responses.
    Nat Rev Immunol. 2009 Aug;9(8):581-93 PMID: 19498381
  145. Phosphatidylserine directly and positively regulates fusion of myoblasts into myotubes.
    Biochem Biophys Res Commun. 2011 Oct 14;414(1):9-13 PMID: 21910971
  146. Integrin reconstituted in GUVs: a biomimetic system to study initial steps of cell spreading.
    Biochim Biophys Acta. 2009 Oct;1788(10):2291-300 PMID: 19665445
  147. Exosomes/microvesicles: mediators of cancer-associated immunosuppressive microenvironments.
    Semin Immunopathol. 2011 Sep;33(5):441-54 PMID: 21688197
  148. Nonspecific B and T cell-stimulatory activity mediated by mast cells is associated with exosomes.
    Int Arch Allergy Immunol. 2001 Jan-Mar;124(1-3):133-6 PMID: 11306949
  149. Production of membrane proteins using cell-free expression systems.
    Proteomics. 2008 Oct;8(19):3933-46 PMID: 18763710
  150. Intercellular transfer of the oncogenic receptor EGFRvIII by microvesicles derived from tumour cells.
    Nat Cell Biol. 2008 May;10(5):619-24 PMID: 18425114
  151. Proteomics analysis of A33 immunoaffinity-purified exosomes released from the human colon tumor cell line LIM1215 reveals a tissue-specific protein signature.
    Mol Cell Proteomics. 2010 Feb;9(2):197-208 PMID: 19837982
  152. Therapeutic microRNA delivery suppresses tumorigenesis in a murine liver cancer model.
    Cell. 2009 Jun 12;137(6):1005-17 PMID: 19524505
  153. Proteomic profiling of human plasma exosomes identifies PPARgamma as an exosome-associated protein.
    Biochem Biophys Res Commun. 2009 Jan 16;378(3):433-8 PMID: 19028452
  154. ICAM-1: getting a grip on leukocyte adhesion.
    J Immunol. 2011 May 1;186(9):5021-3 PMID: 21505213
  155. Identification of host proteins associated with retroviral vector particles by proteomic analysis of highly purified vector preparations.
    J Virol. 2008 Feb;82(3):1107-17 PMID: 18032515
  156. Targeting microRNAs involved in human diseases: a novel approach for modification of gene expression and drug development.
    Biochem Pharmacol. 2011 Nov 15;82(10):1416-29 PMID: 21864506
  157. Expulsion of small molecules in vesicles shed by cancer cells: association with gene expression and chemosensitivity profiles.
    Cancer Res. 2003 Aug 1;63(15):4331-7 PMID: 12907600
  158. Proteomic analysis of exosomes isolated from human malignant pleural effusions.
    Am J Respir Cell Mol Biol. 2004 Jul;31(1):114-21 PMID: 14975938
  159. Microvesicles and exosomes: opportunities for cell-derived membrane vesicles in drug delivery.
    J Control Release. 2012 Jul 20;161(2):635-44 PMID: 22138068
  160. Exosomes--vesicular carriers for intercellular communication.
    Curr Opin Cell Biol. 2009 Aug;21(4):575-81 PMID: 19442504
  161. Exosome targeting of tumor antigens expressed by cancer vaccines can improve antigen immunogenicity and therapeutic efficacy.
    Cancer Res. 2011 Aug 1;71(15):5235-44 PMID: 21670078
  162. Uptake of liposomes by cultured mouse bone marrow macrophages: influence of liposome composition and size.
    Biochim Biophys Acta. 1991 Jan 9;1061(1):56-64 PMID: 1995057
  163. Activation of macrophages by P2X7-induced microvesicles from myeloid cells is mediated by phospholipids and is partially dependent on TLR4.
    J Immunol. 2010 Sep 15;185(6):3740-9 PMID: 20709956
  164. Roles of lipid polymorphism in intracellular delivery.
    Adv Drug Deliv Rev. 2001 Apr 25;47(2-3):139-48 PMID: 11311989
  165. Antigen-presenting cell exosomes are protected from complement-mediated lysis by expression of CD55 and CD59.
    Eur J Immunol. 2003 Feb;33(2):522-31 PMID: 12645951
  166. Expression and characterization of recombinant human milk fat globule-EGF factor VIII.
    Int J Mol Med. 2011 Dec;28(6):1071-6 PMID: 21874225
  167. Exosomes released during reticulocyte maturation bind to fibronectin via integrin alpha4beta1.
    Eur J Biochem. 2000 Jan;267(2):583-90 PMID: 10632729
  168. Distinct roles for tetraspanins CD9, CD63 and CD81 in the formation of multinucleated giant cells.
    Immunology. 2009 Jun;127(2):237-48 PMID: 19489128
  169. Functional analyses of two cellular binding domains of bovine lactadherin.
    Biochemistry. 2000 May 23;39(20):6200-6 PMID: 10821695
  170. The clearance of apoptotic cells: implications for autoimmunity.
    Autoimmun Rev. 2002 May;1(3):154-61 PMID: 12849009
  171. Human tumor virus utilizes exosomes for intercellular communication.
    Proc Natl Acad Sci U S A. 2010 Nov 23;107(47):20370-5 PMID: 21059916
  172. Indirect activation of naïve CD4+ T cells by dendritic cell-derived exosomes.
    Nat Immunol. 2002 Dec;3(12):1156-62 PMID: 12426563
  173. MicroRNAs: novel biomarkers for human cancer.
    Clin Chem. 2009 Apr;55(4):623-31 PMID: 19246618
  174. Secretion of active membrane type 1 matrix metalloproteinase (MMP-14) into extracellular space in microvesicular exosomes.
    J Cell Biochem. 2008 Dec 1;105(5):1211-8 PMID: 18802920
  175. Astrocytes and Glioblastoma cells release exosomes carrying mtDNA.
    J Neural Transm (Vienna). 2010 Jan;117(1):1-4 PMID: 19680595
  176. Adhesion and signaling by B cell-derived exosomes: the role of integrins.
    FASEB J. 2004 Jun;18(9):977-9 PMID: 15059973
  177. Circulating microRNAs as stable blood-based markers for cancer detection.
    Proc Natl Acad Sci U S A. 2008 Jul 29;105(30):10513-8 PMID: 18663219
  178. Tetraspanins CD9 and CD81 modulate HIV-1-induced membrane fusion.
    J Immunol. 2006 Oct 15;177(8):5129-37 PMID: 17015697
  179. Membrane properties of sphingomyelins.
    FEBS Lett. 2002 Oct 30;531(1):33-7 PMID: 12401199
  180. Tetraspanin proteins mediate cellular penetration, invasion, and fusion events and define a novel type of membrane microdomain.
    Annu Rev Cell Dev Biol. 2003;19:397-422 PMID: 14570575
  181. Circulating microparticles in cardiovascular disease: implications for atherogenesis and atherothrombosis.
    J Thromb Haemost. 2010 Nov;8(11):2358-68 PMID: 20695980
  182. Cell surface tetraspanin Tspan8 contributes to molecular pathways of exosome-induced endothelial cell activation.
    Cancer Res. 2010 Feb 15;70(4):1668-78 PMID: 20124479
  183. Determination of the binding specificity of an integral membrane protein by saturation transfer difference NMR: RGD peptide ligands binding to integrin alphaIIbbeta3.
    J Med Chem. 2001 Sep 13;44(19):3059-65 PMID: 11543674
  184. Molecular characterization of dendritic cell-derived exosomes. Selective accumulation of the heat shock protein hsc73.
    J Cell Biol. 1999 Nov 1;147(3):599-610 PMID: 10545503
  185. Anti-microRNA-222 (anti-miR-222) and -181B suppress growth of tamoxifen-resistant xenografts in mouse by targeting TIMP3 protein and modulating mitogenic signal.
    J Biol Chem. 2011 Dec 9;286(49):42292-42302 PMID: 22009755
  186. Tumor apoptotic bodies inhibit CTL responses and antitumor immunity via membrane-bound transforming growth factor-beta1 inducing CD8+ T-cell anergy and CD4+ Tr1 cell responses.
    Cancer Res. 2009 Oct 1;69(19):7756-66 PMID: 19789353
  187. Proteomic profiling of exosomes: current perspectives.
    Proteomics. 2008 Oct;8(19):4083-99 PMID: 18780348
  188. Membrane-derived microvesicles: important and underappreciated mediators of cell-to-cell communication.
    Leukemia. 2006 Sep;20(9):1487-95 PMID: 16791265
  189. Improved therapeutic responses for liposomal doxorubicin targeted via thrombospondin peptidomimetics versus untargeted doxorubicin.
    J Pept Sci. 2010 Jul;16(7):315-21 PMID: 20552567
  190. Mast cell-dependent B and T lymphocyte activation is mediated by the secretion of immunologically active exosomes.
    J Immunol. 2001 Jan 15;166(2):868-76 PMID: 11145662
  191. Delivery of therapeutic RNAi by nanovehicles.
    Chembiochem. 2009 Oct 12;10(15):2449-54 PMID: 19688785
  192. 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 Sep;140(3):455-62 PMID: 2777884
  193. Endosome-to-cytosol transport of viral nucleocapsids.
    Nat Cell Biol. 2005 Jul;7(7):653-64 PMID: 15951806
  194. Characterization of extracellular circulating microRNA.
    Nucleic Acids Res. 2011 Sep 1;39(16):7223-33 PMID: 21609964
  195. Identification and proteomic profiling of exosomes in human urine.
    Proc Natl Acad Sci U S A. 2004 Sep 7;101(36):13368-73 PMID: 15326289
  196. Phosphatidylserine targeting for diagnosis and treatment of human diseases.
    Apoptosis. 2010 Sep;15(9):1072-82 PMID: 20440562
Article Info
Journal
International journal of nanomedicine
Abbr.
Int J Nanomedicine
ISSN
1178-2013
DOI
10.2147/IJN.S29661
Published
2012-00-00
Epub
2012-00-16
Pages
1525-41
Language
English
Region
New Zealand
NLM ID
101263847
PMCID
PMC3356169
Subset
IM
Grants
European Research Council · 260627 · International
External Links
PubMed source DOI: 10.2147/IJN.S29661 PMC Full Text View journal details
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