Biodistribution of Therapeutic Extracellular Vesicles

Overview

Journal Extracell Vesicles Circ Nucl Acids

Date 2024 Dec 19

PMID 39697988

Authors

Dhanu Gupta

Oscar P B Wiklander

Matthew J A Wood

Samir El-Andaloussi

Affiliations

Soon will be listed here.

Abstract

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

References

Mendt M, Kamerkar S, Sugimoto H, McAndrews K, Wu C, Gagea M . Generation and testing of clinical-grade exosomes for pancreatic cancer. JCI Insight. 2018; 3(8). PMC: 5931131. DOI: 10.1172/jci.insight.99263. View

Thompson C, Purushothaman A, Ramani V, Vlodavsky I, Sanderson R . Heparanase regulates secretion, composition, and function of tumor cell-derived exosomes. J Biol Chem. 2013; 288(14):10093-10099. PMC: 3617250. DOI: 10.1074/jbc.C112.444562. View

Rana S, Yue S, Stadel D, Zoller M . Toward tailored exosomes: the exosomal tetraspanin web contributes to target cell selection. Int J Biochem Cell Biol. 2012; 44(9):1574-84. DOI: 10.1016/j.biocel.2012.06.018. View

McNamara R, Dittmer D . Modern Techniques for the Isolation of Extracellular Vesicles and Viruses. J Neuroimmune Pharmacol. 2019; 15(3):459-472. PMC: 7065924. DOI: 10.1007/s11481-019-09874-x. View

Ghosh A, Davey M, Chute I, Griffiths S, Lewis S, Chacko S . 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. PMC: 4201556. DOI: 10.1371/journal.pone.0110443. View

Oksvold M, Neurauter A, Pedersen K . Magnetic bead-based isolation of exosomes. Methods Mol Biol. 2014; 1218:465-81. DOI: 10.1007/978-1-4939-1538-5_27. View

Gallart-Palau X, Serra A, Wong A, Sandin S, Lai M, Chen C . Extracellular vesicles are rapidly purified from human plasma by PRotein Organic Solvent PRecipitation (PROSPR). Sci Rep. 2015; 5:14664. PMC: 4588595. DOI: 10.1038/srep14664. View

Duijvesz D, Versluis C, van der Fels C, den Berg M, Leivo J, Peltola M . Immuno-based detection of extracellular vesicles in urine as diagnostic marker for prostate cancer. Int J Cancer. 2015; 137(12):2869-78. DOI: 10.1002/ijc.29664. View

Mitchell M, Billingsley M, Haley R, Wechsler M, Peppas N, Langer R . Engineering precision nanoparticles for drug delivery. Nat Rev Drug Discov. 2020; 20(2):101-124. PMC: 7717100. DOI: 10.1038/s41573-020-0090-8. View

10.

Nolan J, Duggan E . Analysis of Individual Extracellular Vesicles by Flow Cytometry. Methods Mol Biol. 2017; 1678:79-92. DOI: 10.1007/978-1-4939-7346-0_5. View

11.

Turner M, Balu-Iyer S . Challenges and Opportunities for the Subcutaneous Delivery of Therapeutic Proteins. J Pharm Sci. 2018; 107(5):1247-1260. PMC: 5915922. DOI: 10.1016/j.xphs.2018.01.007. View

12.

Whittaker T, Nagelkerke A, Nele V, Kauscher U, Stevens M . Experimental artefacts can lead to misattribution of bioactivity from soluble mesenchymal stem cell paracrine factors to extracellular vesicles. J Extracell Vesicles. 2020; 9(1):1807674. PMC: 7480412. DOI: 10.1080/20013078.2020.1807674. View

13.

Nolte-t Hoen E, van der Vlist E, Aalberts M, Mertens H, Bosch B, Bartelink W . Quantitative and qualitative flow cytometric analysis of nanosized cell-derived membrane vesicles. Nanomedicine. 2011; 8(5):712-20. PMC: 7106164. DOI: 10.1016/j.nano.2011.09.006. View

14.

Lazaro-Ibanez E, Faruqu F, Saleh A, Silva A, Wang J, Rak J . Selection of Fluorescent, Bioluminescent, and Radioactive Tracers to Accurately Reflect Extracellular Vesicle Biodistribution . ACS Nano. 2021; 15(2):3212-3227. PMC: 7905875. DOI: 10.1021/acsnano.0c09873. View

15.

Imai T, Takahashi Y, Nishikawa M, Kato K, Morishita M, Yamashita T . Macrophage-dependent clearance of systemically administered B16BL6-derived exosomes from the blood circulation in mice. J Extracell Vesicles. 2015; 4:26238. PMC: 4323410. DOI: 10.3402/jev.v4.26238. View

16.

Cheng L, Zhang X, Tang J, Lv Q, Liu J . Gene-engineered exosomes-thermosensitive liposomes hybrid nanovesicles by the blockade of CD47 signal for combined photothermal therapy and cancer immunotherapy. Biomaterials. 2021; 275:120964. DOI: 10.1016/j.biomaterials.2021.120964. View

17.

Somiya M, Kuroda S . Reporter gene assay for membrane fusion of extracellular vesicles. J Extracell Vesicles. 2021; 10(13):e12171. PMC: 8607979. DOI: 10.1002/jev2.12171. View

18.

Sork H, Conceicao M, Corso G, Nordin J, Lee Y, Krjutskov K . Profiling of Extracellular Small RNAs Highlights a Strong Bias towards Non-Vesicular Secretion. Cells. 2021; 10(6). PMC: 8235078. DOI: 10.3390/cells10061543. View

19.

Jia G, Han Y, An Y, Ding Y, He C, Wang X . NRP-1 targeted and cargo-loaded exosomes facilitate simultaneous imaging and therapy of glioma in vitro and in vivo. Biomaterials. 2018; 178:302-316. DOI: 10.1016/j.biomaterials.2018.06.029. View

20.

Aird W . Phenotypic heterogeneity of the endothelium: I. Structure, function, and mechanisms. Circ Res. 2007; 100(2):158-73. DOI: 10.1161/01.RES.0000255691.76142.4a. View