Abstract

Extracellular vesicles (EVs) are sophisticated and sensitive messengers released by cells to communicate with and influence distant and neighboring cells via selective transfer of bioactive content, including protein lipids and nucleic acids. EVs have therefore attracted broad interest as new and refined potential therapeutic systems in many diseases, including cancer, due to their low immunogenicity, non-toxicity, and elevated bioavailability. They might serve as safe and effective vehicles for the transport of therapeutic molecules to specific tissues and cells. In this review, we focus on EVs as a vehicle for gene therapy in cancer. We describe recent developments in EV engineering to achieve efficient intracellular delivery of cancer therapeutics and avoid off-target effects, to provide an overview of the potential applications of EV-mediated gene therapy and the most promising biomedical advances.

Highlights

  • Extracellular vesicles (EVs) are nanoscale particles released by producing cells in the extracellular environment to interact with and act on distant and neighboring cells

  • We focus on EVs as a vehicle for gene therapy in cancer

  • We describe the potential use of EVs as a tool for therapeutic nucleic acid delivery to target cells, to improve treatment efficacy and avoid side effects

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Summary

Introduction

Extracellular vesicles (EVs) are nanoscale particles released by producing cells in the extracellular environment to interact with and act on distant and neighboring cells. The MSC-EVs are widely used as therapeutic agents for different immunological disorders [26] and their use has shown incredibly promising results in clinical trials on severe forms of graft-versus-host disease (GvHD; Grade II–IV) [27]; chronic kidney diseases [28]; and Type I Diabetes Mellitus (T1DM) [29]. Another example of how EVs are able to negatively regulate immunoresponse is given by immature dendritic cell (DC)-derived EVs devoid of immunostimulatory molecules (MHC-I and -II) [30] and carrying co-regulatory proteins that suppress immune reactions. Immature DCs were described as a major source of EVs [57] and as innovative cell-free vaccines, reverting cancer immune escape [58,59,60]

EV Loading Methods
Parental Cell-Based Engineering
Engineering EV-Based Cancer Therapy
Solid Tumors
Hematologic Tumors
Findings
Conclusions

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