Skip to main content

Exosomes in Drug Delivery

  • Chapter
  • First Online:
Role of Exosomes in Biological Communication Systems

Abstract

A tremendous number of therapeutic molecules and vaccines have been generated in the last few decades. This level of production necessitates an effective and safe drug delivery system (DDS). Designing a DDS for the specific targeting of organs and for passing through the blood-brain barrier remains a challenge. Several drug carriers have been tested, such as silver- and gold-coated nanoparticles, liposomes and exosomes. Among these, exosomes have received much attention due to their natural composition, outstanding safety and efficient crossing of the blood-brain barrier. A considerable number of studies, including clinical trials, have described the use of exosomes as vehicles for several drug constituents, such as proteins, small molecules, ribonucleic acids (RNAs) and deoxyribonucleic acid (DNA). Despite great accomplishments in the application of exosomes, many challenges, such as induced cytotoxicity, undesired interactions and the production of sufficient quantities for clinical use require further research. In the current chapter, a number of issues regarding the use of exosomes for drug delivery are discussed. The composition, characterization and functions of exosomes are reviewed. We focus on exosomes as vehicles for delivering different drug molecules. In addition, the major advantages and disadvantages associated with the use of exosomes as therapeutic drug vehicles are addressed.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

ATP:

Adenosine triphosphate

BACE1:

Beta-secretase 1

BBB:

Blood-brain barrier

C1C2:

Claudin-1 derived peptide

cDNA:

Complementary deoxyribonucleic acid

CPP:

Cell-penetrating peptide

DDS:

Drug delivery system

DLS:

Dynamic light scattering

DNA:

Deoxyribonucleic acid

EGFR:

Epidermal growth factor receptor

EPR:

Enhanced permeability and retention

FDA:

Food and Drug Administration

GM3:

Monosialodihexosylganglioside

HGF:

Hepatocyte growth factor

HMG-17:

High-mobility group protein 17

IFN-γ:

Interferon-gamma

ILVs:

Intraluminal vesicles

ISEV:

International Society for Extracellular Vesicles

Lamp2b-IL3:

Lysosomal-associated membrane protein 2b-interlukin 3

LDHB:

Lactate dehydrogenase B

LT:

Leukotriene

MHC:

Major histocompatibility complex

miRNA:

MicroRNA

mRNA:

Messenger ribonucleic acid

MS:

Mass spectrometry

MVBs:

Multivesicular bodies

ng:

Nanogram

nm:

Nanometer

PBMC:

Peripheral blood mononuclear cell

PD:

Parkinson’s disease

PEG:

Polyethylene glycol

PS:

Phosphatidylserine

Rab:

Ras-related protein

RNA:

Ribonucleic acid

siRNA:

Small interfering ribonucleic acid

SM:

Sphingomyelin

TEXs:

Tumour-derived exosomes

TSG101:

Tumour susceptibility gene 101

VEGF:

Vascular endothelial growth factor

References

  • Abrami L, Brandi L, Moayeri M et al (2013) Hijacking multivesicular bodies enables long-term and exosome-mediated long-distance action of anthrax toxin. Cell Rep 5:986–996

    Article  CAS  PubMed  Google Scholar 

  • Agrawal AK, Aqil F, Jeyabalan J et al (2017) Milk-derived exosomes for oral delivery of paclitaxel. Nanomedicine 13:1627–1636

    Article  CAS  PubMed  Google Scholar 

  • Al-Dosari MS, Gao X (2009) Nonviral gene delivery: principle, limitations, and recent progress. AAPS J 11:671–681

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Allen TM, Cullis PR (2013) Liposomal drug delivery systems: from concept to clinical applications. Adv Drug Deliv Rev 65:36–48

    Article  CAS  PubMed  Google Scholar 

  • Alshehri A, Grabowska A, Stolnik S (2018) Pathways of cellular internalisation of liposomes delivered siRNA and effects on siRNA engagement with target mRNA and silencing in cancer cells. Sci Rep 8:3748

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Alvarez-Erviti L, Seow Y, Yin H, Betts C, Lakhal S, Wood MJ (2011) Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat Biotechnol 29:341

    Article  CAS  PubMed  Google Scholar 

  • Anand P, Sundaram C, Jhurani S, Kunnumakkara AB, Aggarwal BB (2008) Curcumin and cancer: an “old-age” disease with an “age-old” solution. Cancer Lett 267:133–164

    Article  CAS  PubMed  Google Scholar 

  • Andaloussi SE, Mäger I, Breakefield XO, Wood MJ (2013) Extracellular vesicles: biology and emerging therapeutic opportunities. Nat Rev Drug Discov 12:347–357

    Article  CAS  Google Scholar 

  • Antimisiaris SG, Mourtas S, Marazioti A (2018) Exosomes and exosome-inspired vesicles for targeted drug delivery. Pharmaceutics 10:218

    Article  CAS  PubMed Central  Google Scholar 

  • Arslan F, Lai RC, Smeets MB et al (2013) Mesenchymal stem cell-derived exosomes increase ATP levels, decrease oxidative stress and activate PI3K/Akt pathway to enhance myocardial viability and prevent adverse remodeling after myocardial ischemia/reperfusion injury. Stem Cell Res 10:301–312

    Article  CAS  PubMed  Google Scholar 

  • Balachandran B, Yuana Y (2019) Extracellular vesicles-based drug delivery system for cancer treatment. Cogent Med 6:1–23

    Article  Google Scholar 

  • Banizs AB, Huang T, Dryden K et al (2014) In vitro evaluation of endothelial exosomes as carriers for small interfering ribonucleic acid delivery. Int J Nanomed 9:4223

    CAS  Google Scholar 

  • Bartel DP (2009) MicroRNAs: target recognition and regulatory functions. Cell 136:215–233

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Barth RJ Jr, Mulé JJ, Spiess PJ, Rosenberg SA (1991) Interferon gamma and tumor necrosis factor have a role in tumor regressions mediated by murine CD8+ tumor-infiltrating lymphocytes. J Exp Med 173:647–658

    Article  CAS  PubMed  Google Scholar 

  • Batrakova EV, Kim MS (2015) Using exosomes, naturally-equipped nanocarriers, for drug delivery. J Controlled Release 219:396–405

    Article  CAS  Google Scholar 

  • Bhatnagar S, Shinagawa K, Castellino FJ, Schorey JS (2007) Exosomes released from macrophages infected with intracellular pathogens stimulate a proinflammatory response in vitro and in vivo. Blood 110:3234–3244

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bunggulawa EJ, Wang W, Yin T et al (2018) Recent advancements in the use of exosomes as drug delivery systems. J Nanobiotechnol 16:1–13

    Article  CAS  Google Scholar 

  • Camussi G, Deregibus M-C, Bruno S, Grange C, Fonsato V, Tetta C (2011) Exosome/microvesicle-mediated epigenetic reprogramming of cells. Am J Cancer Res 1:98

    PubMed  Google Scholar 

  • Chen T, Guo J, Yang M, Zhu X, Cao X (2011) Chemokine-containing exosomes are released from heat-stressed tumor cells via lipid raft-dependent pathway and act as efficient tumor vaccine. J Immunol 186:2219–2228

    Article  CAS  PubMed  Google Scholar 

  • Clayton A, Turkes A, Navabi H, Mason MD, Tabi Z (2005) Induction of heat shock proteins in B-cell exosomes. J Cell Sci 118:3631–3638

    Article  CAS  PubMed  Google Scholar 

  • Conigliaro A, Cicchini C (2019) Exosome-mediated signaling in epithelial to mesenchymal transition and tumor progression. J Clin Med 8:26

    Article  CAS  Google Scholar 

  • D'Asti E, Garnier D, Lee TH, Montermini L, Meehan B, Rak J (2012) Oncogenic extracellular vesicles in brain tumor progression. Front Physiol 3:294

    PubMed  PubMed Central  Google Scholar 

  • Duijvesz D, Luider T, Bangma CH, Jenster G (2011) Exosomes as biomarker treasure chests for prostate cancer. Eur Urol 59:823–831

    Article  CAS  PubMed  Google Scholar 

  • Esser J, Gehrmann U, D'Alexandri FL et al (2010) Exosomes from human macrophages and dendritic cells contain enzymes for leukotriene biosynthesis and promote granulocyte migration. J Allergy Clin Immunol 126:1032–1040

    Article  CAS  PubMed  Google Scholar 

  • Ewert KK, Zidovska A, Ahmad A et al (2010) Cationic liposome–nucleic acid complexes for gene delivery and silencing: pathways and mechanisms for plasmid DNA and siRNA. Top Curr Chem 296:191–226

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fuhrmann G, Serio A, Mazo M, Nair R, Stevens MM (2015) Active loading into extracellular vesicles significantly improves the cellular uptake and photodynamic effect of porphyrins. J Control Release 205:35–44

    Article  CAS  PubMed  Google Scholar 

  • Goh WJ, Zou S, Ong WY et al (2017) Bioinspired cell-derived nanovesicles versus exosomes as drug delivery systems: a cost-effective alternative. Sci Rep 7:14322

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Gregoriadis G, Ryman B (1971) Liposomes as carriers of enzymes or drugs: a new approach to the treatment of storage diseases. Biochem J 124:58P

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gustafson HH, Holt-Casper D, Grainger DW, Ghandehari H (2015) Nanoparticle uptake: the phagocyte problem. Nano Today 10:487–510

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ha D, Yang N, Nadithe V (2016) Exosomes as therapeutic drug carriers and delivery vehicles across biological membranes: current perspectives and future challenges. Acta Pharm Sin B 6:287–296

    Article  PubMed  PubMed Central  Google Scholar 

  • Hacein-Bey-Abina S, Garrigue A, Wang GP et al (2008) Insertional oncogenesis in 4 patients after retrovirus-mediated gene therapy of SCID-X1. J Clin Invest 118:3132–3142

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hadla M, Palazzolo S, Corona G et al (2016) Exosomes increase the therapeutic index of doxorubicin in breast and ovarian cancer mouse models. Nanomedicine 11:2431–2441

    Article  CAS  PubMed  Google Scholar 

  • Haney MJ, Zhao Y, Harrison EB et al (2013) Specific transfection of inflamed brain by macrophages: a new therapeutic strategy for neurodegenerative diseases. PLoS One 8:e61852

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Haney MJ, Klyachko NL, Zhao Y et al (2015) Exosomes as drug delivery vehicles for Parkinson’s disease therapy. J Control Release 207:18–30

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hewson C, Capraro D, Burdach J, Whitaker N, Morris KV (2016) Extracellular vesicle associated long non-coding RNAs functionally enhance cell viability. Noncoding RNA Res 1:3–11

    Article  PubMed  PubMed Central  Google Scholar 

  • Holkers M, Maggio I, Henriques SF, Janssen JM, Cathomen T, Gonçalves MA (2014) Adenoviral vector DNA for accurate genome editing with engineered nucleases. Nat Methods 11:1051

    Article  CAS  PubMed  Google Scholar 

  • Hong Y, Kim YK, Kim GB et al (2019) Degradation of tumour stromal hyaluronan by small extracellular vesicle-PH20 stimulates CD103+ dendritic cells and in combination with PD-L1 blockade boosts anti-tumour immunity. J Extracell Vesicles 8:1670893

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huang X, Yuan T, Tschannen M et al (2013) Characterization of human plasma-derived exosomal RNAs by deep sequencing. BMC Genomics 14:319

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • James Graham Brown Cancer Center, University of Louisville (2011) Study investigating the ability of plant exosomes to deliver curcumin to normal and colon cancer tissue

    Google Scholar 

  • Jia S, Zocco D, Samuels ML et al (2014) Emerging technologies in extracellular vesicle-based molecular diagnostics. Expert Rev Mol Diagn 14:307–321

    Article  CAS  PubMed  Google Scholar 

  • Jiang X-C, Gao J-Q (2017) Exosomes as novel bio-carriers for gene and drug delivery. Int J Pharm 521:167–175

    Article  CAS  PubMed  Google Scholar 

  • Jin L, Zeng X, Liu M, Deng Y, He N (2014) Current progress in gene delivery technology based on chemical methods and nano-carriers. Theranostics 4:240

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Johnsen KB, Gudbergsson JM, Skov MN et al (2016) Evaluation of electroporation-induced adverse effects on adipose-derived stem cell exosomes. Cytotechnology 68:2125–2138

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ju S, Mu J, Dokland T et al (2013) Grape exosome-like nanoparticles induce intestinal stem cells and protect mice from DSS-induced colitis. Mol Ther 21:1345–1357

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim MS, Haney MJ, Zhao Y et al (2016) Development of exosome-encapsulated paclitaxel to overcome MDR in cancer cells. Nanomedicine 12:655–664

    Article  CAS  PubMed  Google Scholar 

  • Kogure T, Yan IK, Lin W-L, Patel T (2013) Extracellular vesicle–mediated transfer of a novel long noncoding RNA TUC339: a mechanism of intercellular signaling in human hepatocellular cancer. Genes Cancer 4:261–272

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Koh E, Lee EJ, Nam G-H et al (2017) Exosome-SIRPα, a CD47 blockade increases cancer cell phagocytosis. Biomaterials 121:121–129

    Article  CAS  PubMed  Google Scholar 

  • Kooijmans SA, Vader P, van Dommelen SM, van Solinge WW, Schiffelers RM (2012) Exosome mimetics: a novel class of drug delivery systems. Int J Nanomed 7:1525

    CAS  Google Scholar 

  • Lai RC, Arslan F, Lee MM et al (2010) Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury. Stem Cell Res 4:214–222

    Article  CAS  PubMed  Google Scholar 

  • Lai RC, Yeo RWY, Tan KH, Lim SK (2013) Exosomes for drug delivery—a novel application for the mesenchymal stem cell. Biotechnol Adv 31:543–551

    Article  CAS  PubMed  Google Scholar 

  • Lai CP, Mardini O, Ericsson M et al (2014) Dynamic biodistribution of extracellular vesicles in vivo using a multimodal imaging reporter. ACS Nano 8:483–494

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lötvall, J, Hill, AF, Hochberg, F et al. (2014) Minimal experimental requirements for definition of extracellular vesicles and their functions: a position statement from the International Society for Extracellular Vesicles. J Extracell Vesicles 3. https://doi.org/10.3402/jev.v3.26913

  • Lou G, Song X, Yang F et al (2015) Exosomes derived from miR-122-modified adipose tissue-derived MSCs increase chemosensitivity of hepatocellular carcinoma. J Hematol Oncol 8:122

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lu M, Zhao X, Xing H et al (2018) Comparison of exosome-mimicking liposomes with conventional liposomes for intracellular delivery of siRNA. Int J Pharm 550:100–113

    Article  CAS  PubMed  Google Scholar 

  • Luan X, Sansanaphongpricha K, Myers I, Chen H, Yuan H, Sun D (2017) Engineering exosomes as refined biological nanoplatforms for drug delivery. Acta Pharmacol Sin 38:754

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Marcus ME, Leonard JN (2013) FedExosomes: engineering therapeutic biological nanoparticles that truly deliver. Pharmaceuticals 6:659–680

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mashouri L, Yousefi H, Aref AR, Mohammad Ahadi A, Molaei F, Alahari SK (2019) Exosomes: composition, biogenesis, and mechanisms in cancer metastasis and drug resistance. Mol Cancer 18:75

    Article  PubMed  PubMed Central  Google Scholar 

  • Mathivanan S, Ji H, Simpson RJ (2010) Exosomes: extracellular organelles important in intercellular communication. J Proteomics 73:1907–1920

    Article  CAS  PubMed  Google Scholar 

  • Mathivanan S, Fahner CJ, Reid GE, Simpson RJ (2011) ExoCarta 2012: database of exosomal proteins, RNA and lipids. Nucleic Acids Res 40:D1241–D1D44

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Matsumura Y, Maeda H (1986) A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. Cancer Res 46:6387–6392

    CAS  PubMed  Google Scholar 

  • Mendt M, Kamerkar S, Sugimoto H et al (2018) Generation and testing of clinical-grade exosomes for pancreatic cancer. JCI Insight 3(8):e99263

    Article  PubMed Central  Google Scholar 

  • Nolte EN, Buschow SI, Anderton SM, Stoorvogel W, Wauben MH (2009) Activated T cells recruit exosomes secreted by dendritic cells via LFA-1. Blood 113:1977–1981

    Article  CAS  Google Scholar 

  • Obermeier B, Daneman R, Ransohoff RM (2013) Development, maintenance and disruption of the blood-brain barrier. Nat Med 19:1584

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ohno S-i, Takanashi M, Sudo K et al (2013) Systemically injected exosomes targeted to EGFR deliver antitumor microRNA to breast cancer cells. Mol Ther 21:185–191

    Article  CAS  PubMed  Google Scholar 

  • Pardridge WM (2015) Blood–brain barrier endogenous transporters as therapeutic targets: a new model for small molecule CNS drug discovery. Expert Opin Ther Targets 19:1059–1072

    Article  CAS  PubMed  Google Scholar 

  • Pascucci L, Ceccarelli P, Cocce V et al (2014) 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 192:262–270

    Article  CAS  PubMed  Google Scholar 

  • Patil YP, Jadhav S (2014) Novel methods for liposome preparation. Chem Phys Lipids 177:8–18

    Article  CAS  PubMed  Google Scholar 

  • Patra JK, Das G, Fraceto LF et al (2018) Nano based drug delivery systems: recent developments and future prospects. J Nanobiotechnol 16:71

    Article  CAS  Google Scholar 

  • Pattni BS, Chupin VV, Torchilin VP (2015) New developments in liposomal drug delivery. Chem Rev 115:10938–10966

    Article  CAS  PubMed  Google Scholar 

  • Perez AT, Domenech GH, Frankel C, Vogel CL (2002) Pegylated liposomal doxorubicin (Doxil®) for metastatic breast cancer: the Cancer Research Network, Inc., experience. Cancer Invest 20:22–29

    Article  CAS  PubMed  Google Scholar 

  • Poliakov A, Spilman M, Dokland T, Amling CL, Mobley JA (2009) Structural heterogeneity and protein composition of exosome-like vesicles (prostasomes) in human semen. Prostate 69:159–167

    Article  PubMed  Google Scholar 

  • Rao Q, Zuo B, Lu Z et al (2016) Tumor-derived exosomes elicit tumor suppression in murine hepatocellular carcinoma models and humans in vitro. Hepatology 64:456–472

    Article  CAS  PubMed  Google Scholar 

  • Ravindran J, Prasad S, Aggarwal BB (2009) Curcumin and cancer cells: how many ways can curry kill tumor cells selectively? AAPS J 11:495–510

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rezaie J, Ajezi S, Avci ÇB et al (2018) Exosomes and their application in biomedical field: difficulties and advantages. Mol Neurobiol 55:3372–3393

    Article  CAS  PubMed  Google Scholar 

  • Romagnoli GG, Zelante BB, Toniolo PA, Migliori IK, Barbuto JA (2014) Dendritic cell-derived exosomes may be a tool for cancer immunotherapy by converting tumor cells into immunogenic targets. Front Immunol 5:692

    PubMed  Google Scholar 

  • Sato YT, Umezaki K, Sawada S et al (2016) Engineering hybrid exosomes by membrane fusion with liposomes. Sci Rep 6:21933

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schmidinger M, Wenzel C, Locker G et al (2001) Pilot study with pegylated liposomal doxorubicin for advanced or unresectable hepatocellular carcinoma. Br J Cancer 85:1850

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Seiden MV, Muggia F, Astrow A et al (2004) A phase II study of liposomal lurtotecan (OSI-211) in patients with topotecan resistant ovarian cancer. Gynecol Oncol 93:229–232

    Article  CAS  PubMed  Google Scholar 

  • Shimaoka M, Kawamoto E, Gaowa A, Okamoto T, Park EJ (2019) Connexins and integrins in exosomes. Cancers 11:106

    Article  CAS  PubMed Central  Google Scholar 

  • Shtam TA, Kovalev RA, Varfolomeeva EY, Makarov EM, Kil YV, Filatov MV (2013) Exosomes are natural carriers of exogenous siRNA to human cells in vitro. Cell Commun Signal 11:88

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Skotland T, Sandvig K, Llorente A (2017) Lipids in exosomes: current knowledge and the way forward. Prog Lipid Res 66:30–41

    Article  CAS  PubMed  Google Scholar 

  • Skubitz KM (2003) Phase II trial of pegylated-liposomal doxorubicin (Doxil™) in sarcoma. Cancer Invest 21:167–176

    Article  CAS  PubMed  Google Scholar 

  • Sun D, Zhuang X, Xiang X et al (2010) A novel nanoparticle drug delivery system: the anti-inflammatory activity of curcumin is enhanced when encapsulated in exosomes. Mol Ther 18:1606–1614

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sun D, Zhuang X, Zhang S et al (2013) Exosomes are endogenous nanoparticles that can deliver biological information between cells. Adv Drug Deliv Rev 65:342–347

    Article  CAS  PubMed  Google Scholar 

  • Sundar S, Jha T, Thakur C, Mishra M, Singh V, Buffels R (2003) Single-dose liposomal amphotericin B in the treatment of visceral leishmaniasis in India: a multicenter study. Clin Infect Dis 37:800–804

    Article  CAS  PubMed  Google Scholar 

  • Tan A, Rajadas J, Seifalian AM (2013) Exosomes as nano-theranostic delivery platforms for gene therapy. Adv Drug Deliv Rev 65:357–367

    Article  CAS  PubMed  Google Scholar 

  • Théry C, Amigorena S, Raposo G, Clayton A (2006) Isolation and characterization of exosomes from cell culture supernatants and biological fluids. Curr Protocols Cell Biol 30:3.22.1–3.22.29

    Article  Google Scholar 

  • Théry C, Ostrowski M, Segura E (2009) Membrane vesicles as conveyors of immune responses. Nature reviews immunology 9:581

    Article  PubMed  CAS  Google Scholar 

  • Tian T, Zhu Y-L, Zhou Y-Y et al (2014) Exosome uptake through clathrin-mediated endocytosis and macropinocytosis and mediating miR-21 delivery. J Biol Chem 289:22258–22267

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • van den Boorn JG, Daßler J, Coch C, Schlee M, Hartmann G (2013) Exosomes as nucleic acid nanocarriers. Adv Drug Deliv Rev 65:331–335

    Article  PubMed  CAS  Google Scholar 

  • van der Meel R, Fens MH, Vader P, van Solinge WW, Eniola-Adefeso O, Schiffelers RM (2014) Extracellular vesicles as drug delivery systems: lessons from the liposome field. J Control Release 195:72–85

    Article  PubMed  CAS  Google Scholar 

  • Van der Pol E, Coumans F, Grootemaat A et al (2014) Particle size distribution of exosomes and microvesicles determined by transmission electron microscopy, flow cytometry, nanoparticle tracking analysis, and resistive pulse sensing. J Thromb Haemost 12:1182–1192

    Article  PubMed  Google Scholar 

  • Van Niel G, Porto-Carreiro I, Simoes S, Raposo G (2006) Exosomes: a common pathway for a specialized function. J Biochem 140:13–21

    Article  CAS  PubMed  Google Scholar 

  • Vasir JK, Labhasetwar V (2008) Quantification of the force of nanoparticle-cell membrane interactions and its influence on intracellular trafficking of nanoparticles. Biomaterials 29:4244–4252

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wahlgren J, Karlson TDL, Brisslert M et al (2012) Plasma exosomes can deliver exogenous short interfering RNA to monocytes and lymphocytes. Nucleic Acids Res 40:e130–ee30

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Waldenström A, Ronquist G (2014) Role of exosomes in myocardial remodeling. Circ Res 114:315–324

    Article  PubMed  CAS  Google Scholar 

  • Wang J, De Veirman K, Faict S et al (2016) Multiple myeloma exosomes establish a favourable bone marrow microenvironment with enhanced angiogenesis and immunosuppression. J Pathol 239:162–173

    Article  CAS  PubMed  Google Scholar 

  • Wolfers J, Lozier A, Raposo G et al (2001) Tumor-derived exosomes are a source of shared tumor rejection antigens for CTL cross-priming. Nat Med 7:297

    Article  CAS  PubMed  Google Scholar 

  • Wubbolts R, Leckie RS, Veenhuizen PT et al (2003) Proteomic and biochemical analyses of human B cell-derived exosomes potential implications for their function and multivesicular body formation. J Biol Chem 278:10963–10972

    Article  CAS  PubMed  Google Scholar 

  • Yameen B, Choi WI, Vilos C, Swami A, Shi J, Farokhzad OC (2014) Insight into nanoparticle cellular uptake and intracellular targeting. J Control Release 190:485–499

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang Y, Chen Y, Zhang F, Zhao Q, Zhong H (2015) Increased anti-tumour activity by exosomes derived from doxorubicin-treated tumour cells via heat stress. Int J Hyperthermia 31:498–506

    Article  CAS  PubMed  Google Scholar 

  • Zeelenberg IS, Ostrowski M, Krumeich S et al (2008) Targeting tumor antigens to secreted membrane vesicles in vivo induces efficient antitumor immune responses. Cancer Res 68:1228–1235

    Article  CAS  PubMed  Google Scholar 

  • Zhang H, Wang Y, Bai M et al (2018) Exosomes serve as nanoparticles to suppress tumor growth and angiogenesis in gastric cancer by delivering hepatocyte growth factor si RNA. Cancer Sci 109:629–641

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang Y, Liu Y, Liu H, Tang WH (2019) Exosomes: biogenesis, biologic function and clinical potential. Cell Biosci 9:19

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhuang X, Xiang X, Grizzle W et al (2011) Treatment of brain inflammatory diseases by delivering exosome encapsulated anti-inflammatory drugs from the nasal region to the brain. Mol Ther 19:1769–1779

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zitvogel L, Regnault A, Lozier A et al (1998) Eradication of established murine tumors using a novel cell-free vaccine: dendritic cell derived exosomes. Nat Med 4:594–600

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank the editors for their support.

Compliance with Ethical Standards: This article does not contain any studies with human participants or animals performed by any of the authors.

Disclosure of Interests: All authors declare they have no conflict of interest.

Funding: The author(s) received no financial support for the research, authorship, and/or publication of this article.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Mohammad N. Alomary .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2021 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Almughem, F.A., Alshehri, A.A., Alomary, M.N. (2021). Exosomes in Drug Delivery. In: Alzahrani, F.A., Saadeldin, I.M. (eds) Role of Exosomes in Biological Communication Systems. Springer, Singapore. https://doi.org/10.1007/978-981-15-6599-1_17

Download citation

Publish with us

Policies and ethics