Imperial College London
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Professor David W. McComb

Faculty of Engineering, Department of Materials

Adjunct Professor
 
 
 
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Contact

 

+44 (0)20 7594 6750d.mccomb Website

 
 
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Location

 

Royal School of MinesSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Ortega-Pineda:2022:10.1002/adhm.202100805,
author = {Ortega-Pineda, L and Sunyecz, A and Salazar-Puerta, AI and Rincon-Benavides, MA and Alzate-Correa, D and Anaparthi, AL and Guilfoyle, E and Mezache, L and Struckman, HL and Duarte-Sanmiguel, S and Deng, B and McComb, DW and Dodd, DJ and Lawrence, WR and Moore, J and Zhang, J and Reátegui, E and Veeraraghavan, R and Nelson, MT and Gallego-Perez, D and Higuita-Castro, N},
doi = {10.1002/adhm.202100805},
journal = {Adv Healthc Mater},
title = {Designer Extracellular Vesicles Modulate Pro-Neuronal Cell Responses and Improve Intracranial Retention.},
url = {http://dx.doi.org/10.1002/adhm.202100805},
volume = {11},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Gene/oligonucleotide therapies have emerged as a promising strategy for the treatment of different neurological conditions. However, current methodologies for the delivery of neurogenic/neurotrophic cargo to brain and nerve tissue are fraught with caveats, including reliance on viral vectors, potential toxicity, and immune/inflammatory responses. Moreover, delivery to the central nervous system is further compounded by the low permeability of the blood brain barrier. Extracellular vesicles (EVs) have emerged as promising delivery vehicles for neurogenic/neurotrophic therapies, overcoming many of the limitations mentioned above. However, the manufacturing processes used for therapeutic EVs remain poorly understood. Here, we conducted a detailed study of the manufacturing process of neurogenic EVs by characterizing the nature of cargo and surface decoration, as well as the transfer dynamics across donor cells, EVs, and recipient cells. Neurogenic EVs loaded with Ascl1, Brn2, and Myt1l (ABM) are found to show enhanced neuron-specific tropism, modulate electrophysiological activity in neuronal cultures, and drive pro-neurogenic conversions/reprogramming. Moreover, murine studies demonstrate that surface decoration with glutamate receptors appears to mediate enhanced EV delivery to the brain. Altogether, the results indicate that ABM-loaded designer EVs can be a promising platform nanotechnology to drive pro-neuronal responses, and that surface functionalization with glutamate receptors can facilitate the deployment of EVs to the brain.
AU  - Ortega-Pineda,L
AU  - Sunyecz,A
AU  - Salazar-Puerta,AI
AU  - Rincon-Benavides,MA
AU  - Alzate-Correa,D
AU  - Anaparthi,AL
AU  - Guilfoyle,E
AU  - Mezache,L
AU  - Struckman,HL
AU  - Duarte-Sanmiguel,S
AU  - Deng,B
AU  - McComb,DW
AU  - Dodd,DJ
AU  - Lawrence,WR
AU  - Moore,J
AU  - Zhang,J
AU  - Reátegui,E
AU  - Veeraraghavan,R
AU  - Nelson,MT
AU  - Gallego-Perez,D
AU  - Higuita-Castro,N
DO  - 10.1002/adhm.202100805
PY  - 2022///
TI  - Designer Extracellular Vesicles Modulate Pro-Neuronal Cell Responses and Improve Intracranial Retention.
T2  - Adv Healthc Mater
UR  - http://dx.doi.org/10.1002/adhm.202100805
UR  - https://www.ncbi.nlm.nih.gov/pubmed/35014204
VL  - 11
ER  -
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