TY - JOUR
T1 - Camouflage strategies for therapeutic exosomes evasion from phagocytosis
AU - Parada, Nicol
AU - Romero-Trujillo, Alfonso
AU - Georges, Nicolás
AU - Alcayaga Miranda, Francisca
N1 - © 2021 The Authors. Published by Elsevier B.V. on behalf of Cairo University.
PY - 2021/7/1
Y1 - 2021/7/1
N2 - 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.
AB - 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.
KW - Biodistribution and pharmacokinetics
KW - Drug delivery
KW - Evasion immune system
KW - Evasion phagocytosis
KW - Exosomes
KW - Small extracellular vesicles
KW - Biodistribution and pharmacokinetics
KW - Drug delivery
KW - Evasion immune system
KW - Evasion phagocytosis
KW - Exosomes
KW - Small extracellular vesicles
UR - http://www.scopus.com/inward/record.url?scp=85100316996&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/61317815-a833-3a68-8f90-cec4b9d14295/
U2 - 10.1016/j.jare.2021.01.001
DO - 10.1016/j.jare.2021.01.001
M3 - Article
C2 - 34194832
AN - SCOPUS:85100316996
SN - 2090-1232
VL - 31
SP - 61
EP - 74
JO - Journal of Advanced Research
JF - Journal of Advanced Research
ER -