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Review
. 2023 Feb;31(1):145-169.
doi: 10.1007/s10787-022-01115-7. Epub 2023 Jan 7.

Exosome engineering in cell therapy and drug delivery

Somaye Sadeghi  1   2 , Fahimeh Ramezani Tehrani  3 , Safa Tahmasebi  4 , Abbas Shafiee  5   6 , Seyed Mahmoud Hashemi  7   8
Affiliations
Review

Exosome engineering in cell therapy and drug delivery

Somaye Sadeghi et al. Inflammopharmacology. 2023 Feb.

Abstract

Cell-derived exosomes have opened new horizons in modern therapy for advanced drug delivery and therapeutic applications, due to their key features such as low immunogenicity, high physicochemical stability, capacity to penetrate into tissues, and the innate capacity to communicate with other cells over long distances. Exosome-based liquid biopsy has been potentially used for the diagnosis and prognosis of a range of disorders. Exosomes deliver therapeutic agents, including immunological modulators, therapeutic drugs, and antisense oligonucleotides to certain targets, and can be used as vaccines, though their clinical application is still far from reality. Producing exosomes on a large-scale is restricted to their low circulation lifetime, weak targeting capacity, and inappropriate controls, which need to be refined before being implemented in practice. Several bioengineering methods have been used for refining therapeutic applications of exosomes and promoting their effectiveness, on the one hand, and addressing the existing challenges, on the other. In the short run, new diagnostic platforms and emerging therapeutic strategies will further develop exosome engineering and therapeutic potential. This requires a thorough analysis of exosome engineering approaches along with their merits and drawbacks, as outlined in this paper. The present study is a comprehensive review of novel techniques for exosome development in terms of circulation time in the body, targeting capacity, and higher drug loading/delivery efficacies.

Keywords: Cargo incorporation; Exosome; Extracellular vesicles; Targeted delivery; Therapeutic applications.

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Conflict of interest statement

The authors have no relevant financial or non-financial interests to disclose and declare no conflict of interest.

Figures

Fig. 1
Fig. 1
Exosome biogenesis and its contents. Exosome formation is a function of endocytic membrane invagination and ILV formation inside cells. Early maturation of endosomes leads to the formation of MVBs which are then delivered to lysosomes to be degraded, or cross through microtubules to be combined with the plasma membrane and release exosomes into the extracellular space. In the process of maturation, exosomal cargos (RNAs, proteins, and lipids) are loaded onto ILV via pathways dependent or independent from ESCRT. Source cell cargos can be further delivered to target cells through fusion of direct membrane, endocytosis, and interaction of receptors with ligands
Fig. 2
Fig. 2
Summary of exosomal modifications to address their limitation. Cell targeting specificity of exosomes with cell/tissue-specific peptides, tumor-specific receptors/ligands, or antibodies/nanobodies for tumor markers can be increased. For imaging or tracking purposes, exosomes with fluorescent protein or those displaying chemicals on the surface are applied. Moreover, exosome modification is found to decrease their chance of being cleared by liver and increase its concentration in circulation and the target tissue. Exosome stability is also promoted via exosome engineering by means of physical or chemical treatment, as well as surface modification, the result of which is enhanced delivery efficiency. A combined application of these methods is likely to boost cell targeting specificity and delivery efficacy
Fig. 3
Fig. 3
Physical treatment methods of exosomes for improving therapeutic efficacy. Cargo loading into exosomes is performed through direct physical treatments. This is further facilitated through exosomal membrane pores generated by surfactant treatment, sonication, and electroporation. In the same vein, during membrane recombination processes, cargo loading is enhanced via extrusion, freeze–thaw treatment, and dialysis
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