Camouflage strategies for therapeutic exosomes evasion from phagocytosis

dc.coverageDOI: 10.1016/j.jare.2021.01.001
dc.creatorParada, Nicol
dc.creatorRomero-Trujillo, Alfonso
dc.creatorGeorges, Nicolás
dc.creatorAlcayaga Miranda, Francisca
dc.date2021
dc.date.accessioned2025-11-18T19:47:24Z
dc.date.available2025-11-18T19:47:24Z
dc.description<p>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.</p>eng
dc.descriptionBackground: 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.spa
dc.identifierhttps://investigadores.uandes.cl/en/publications/4b4a051b-72c1-4f23-b6ae-01e140a57cd3
dc.identifier.urihttps://repositorio.uandes.cl/handle/uandes/55013
dc.languageeng
dc.rightsinfo:eu-repo/semantics/openAccess
dc.sourcevol.31 (2021) date: 2021-07-01 p.61-74
dc.subjectBiodistribution and pharmacokinetics
dc.subjectDrug delivery
dc.subjectEvasion immune system
dc.subjectEvasion phagocytosis
dc.subjectExosomes
dc.subjectSmall extracellular vesicles
dc.subjectBiodistribution and pharmacokinetics
dc.subjectDrug delivery
dc.subjectEvasion immune system
dc.subjectEvasion phagocytosis
dc.subjectExosomes
dc.subjectSmall extracellular vesicles
dc.titleCamouflage strategies for therapeutic exosomes evasion from phagocytosiseng
dc.typeArticleeng
dc.typeArtículospa
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