Camouflage strategies for therapeutic exosomes evasion from phagocytosis

Nicol Parada, Alfonso Romero-Trujillo, Nicolás Georges, Francisca Alcayaga Miranda

Research output: Contribution to journalReview articlepeer-review

Abstract

Background: Even though exosome-based therapy has been shown to be able to control the progression of different pathologies, the data revealed by pharmacokinetic studies warn of the low residence time of exogenous exosomes in circulation that can hinder the clinical translation of therapeutic exosomes. The macrophages related to the organs of the mononuclear phagocytic system are responsible primarily for the rapid clearance and retention of exosomes, which strongly limits the amount of exosomal particles available to reach the target tissue, accumulate in it and release with high efficiency its therapeutic cargo in acceptor target cells to exert the desired biological effect. Aim of review: Endowing exosomes with surface modifications to evade the immune system is a plausible strategy to contribute to the suppression of exosomal clearance and increase the efficiency of their targeted content delivery. Here, we summarize the current evidence about the mechanisms underlying the recognition and sequestration of therapeutic exosomes by phagocytic cells. Also, we propose different strategies to generate 'invisible' exosomes for the immune system, through the incorporation of different anti-phagocytic molecules on the exosomes’ surface that allow increasing the circulating half-life of therapeutic exosomes with the purpose to increase their bioavailability to reach the target tissue, transfer their therapeutic molecular cargo and improve their efficacy profile. Key scientific concepts of review: Macrophage-mediated phagocytosis are the main responsible behind the short half-life in circulation of systemically injected exosomes, hindering their therapeutic effect. Exosomes ‘Camouflage Cloak’ strategy using antiphagocytic molecules can contribute to the inhibition of exosomal clearance, hence, increasing the on-target effect. Some candidate molecules that could exert an antiphagocytic role are CD47, CD24, CD44, CD31, β2M, PD-L1, App1, and DHMEQ. Pre- and post-isolation methods for exosome engineering are compatible with the loading of therapeutic cargo and the expression of antiphagocytic surface molecules.

Original languageEnglish
JournalJournal of Advanced Research
DOIs
StateAccepted/In press - 2021

Bibliographical note

Funding Information:
This work was supported by National Agency for Investigation and Development-ANID, FONDECYT Regular #1190411 to F.A-M.

Funding Information:
The authors specially thank Dr. Maroun Khoury and Dr. Jimena Cuenca (Medicine Faculty, Universidad de los Andes, Santiago, Chile) for their helpful scientific discussions and Mr. Jacob Buckles Price for the English revision of the manuscript. This work was supported by National Agency for Investigation and Development-ANID, FONDECYT Regular #1190411 to F.A-M.

Publisher Copyright:
© 2021

Keywords

  • Biodistribution and pharmacokinetics
  • Drug delivery
  • Evasion immune system
  • Evasion phagocytosis
  • Exosomes
  • Small extracellular vesicles

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