Abstract

Exosomes are lipid bilayer membrane vesicles and are emerging as competent nanocarriers for drug delivery. The clinical translation of exosomes faces many challenges such as massive production, standard isolation, drug loading, stability and quality control. In recent years, artificial exosomes are emerging based on nanobiotechnology to overcome the limitations of natural exosomes. Major types of artificial exosomes include ‘nanovesicles (NVs)’, ‘exosome-mimetic (EM)’ and ‘hybrid exosomes (HEs)’, which are obtained by top-down, bottom-up and biohybrid strategies, respectively. Artificial exosomes are powerful alternatives to natural exosomes for drug delivery. Here, we outline recent advances in artificial exosomes through nanobiotechnology and discuss their strengths, limitations and future perspectives. The development of artificial exosomes holds great values for translational nanomedicine.

Highlights

  • In recent decades, synthetic nanoparticles (NPs) including liposomes [1], micelles [2], dendrimers [3], nanocapsules [4], nanodiamonds [5], nanosponges [6], nanoemulsions [7] and self-assembled peptides [8] have been extensively studied for nanomedicine, for targeted cancer therapy

  • NPs could be functionalized by conjugating with polyethylene glycol (PEG) to increase circulation times [23, 24] and by introducing antibodies or peptides [25, 26] to the surface to enhance the targeting capacity and change biodistribution

  • In view of the shortcomings of natural exosomes, a growing number of studies are aiming to develop artificial exosomes based on top-down, bottom-up or biohybrid technologies

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Summary

Introduction

Synthetic nanoparticles (NPs) including liposomes [1], micelles [2], dendrimers [3], nanocapsules [4], nanodiamonds [5], nanosponges [6], nanoemulsions [7] and self-assembled peptides [8] have been extensively studied for nanomedicine, for targeted cancer therapy. Clinical failure of synthetic NPs may be attributed to the differences in the biological barriers and immune systems between human and animal models [22]. Despite promising results of exosome-mediated drug delivery in murine models, the translation of exosomes is challenged by massive production [38], purification [39], modification [40], drug loading [41] and storage [42]. In view of the shortcomings of natural exosomes, a growing number of studies are aiming to develop artificial exosomes based on top-down, bottom-up or biohybrid technologies. The development of artificial exosomes through nanobiotechnology hold great promises for advanced drug delivery with combined advantages of natural and synthetic NPs [45]. We provide a comprehensive review of recent advances in nanofabrication of these artificial exosomes (Fig. 1) and discuss their challenges and future perspective for translational nanomedicine

Artificial exosomes by nanobiotechnology
Mice primary hepatocytes
Murine embryonic stem cell
Similar size distribution and morphology
Comparison to natural exosomes
Stable structure
Efficient cargo loading targeting
Findings
Natural exosomes
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