Engineered exosomes mediated targeted delivery of neuroprotective peptide NR2B9c for the treatment of traumatic brain injury

Neuroprotection is one of the core treatment strategies for brain injuries including traumatic brain injury (TBI). NR2B9c is a promising neuroprotective peptide but its clinical translation is limited because of poor brain penetrability. Exosomes are naturally occurring nanovesicles having therapeut...

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Veröffentlicht in:International journal of pharmaceutics 2024-01, Vol.649, p.123656-123656, Article 123656
Hauptverfasser: Haroon, Khan, Zheng, Haoran, Wu, Shengju, Liu, Ze, Tang, Yaohui, Yang, Guo-Yuan, Liu, Yingli, Zhang, Zhijun
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container_title International journal of pharmaceutics
container_volume 649
creator Haroon, Khan
Zheng, Haoran
Wu, Shengju
Liu, Ze
Tang, Yaohui
Yang, Guo-Yuan
Liu, Yingli
Zhang, Zhijun
description Neuroprotection is one of the core treatment strategies for brain injuries including traumatic brain injury (TBI). NR2B9c is a promising neuroprotective peptide but its clinical translation is limited because of poor brain penetrability. Exosomes are naturally occurring nanovesicles having therapeutic potential for TBI as well as an efficient drug delivery carrier to the brain. Here, we engineered exosomes with neuron targeting peptide rabies virus glycoprotein (RVG29) via bio-orthogonal click chemistry technique and loaded it with NR2B9c, developing RVG-Exo . RVG29 conjugated exosome had higher neuron targeting efficiency compared to naïve exosomes both in vivo and in vitro. RVG-Exo had great cytoprotective effect against oxygen glucose deprived Neuro2a cells. Intravenous administration of RVG-Exo significantly improved behavioral outcomes and reduced the lesion volume after TBI injury in a mice controlled cortical impact model. Due to their multifunctionality and significant efficacy, we anticipate that RVG-Exo have the potential to be translated both as therapeutic agent as well as cargo delivery system to the brain for the treatment of TBI.
doi_str_mv 10.1016/j.ijpharm.2023.123656
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subjects Animals
Brain
Brain Injuries, Traumatic - drug therapy
Brain Injuries, Traumatic - pathology
Drug Carriers - pharmacology
Exosomes
Mice
Neuroprotection
Peptides
title Engineered exosomes mediated targeted delivery of neuroprotective peptide NR2B9c for the treatment of traumatic brain injury
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