Surface modification of extracellular vesicles with polyoxazolines to enhance their plasma stability and tumor accumulation

L. Simon, J. Constanzo, C. Terraza-Aguirre, Z. Ibn Elfekih, J. Berthelot, B. T. Benkhaled, T. Haute, K. Pednekar, K. Clark, S. J. Emerson, S. Atis, C. Benedetti, S. Langlois, A. Marquant, J. Prakash, A. Wang, J. M. Devoisselle, T. Montier, F. Djouad, J. P. PougetV. Lapinte, Marie Morille*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

9 Citations (Scopus)
1 Downloads (Pure)

Abstract

Extracellular vesicles (EVs) are future promising therapeutics, but their instability in vivo after administration remains an important barrier to their further development. Many groups evaluated EV surface modification strategies to add a targeting group with the aim of controlling EV biodistribution. Conversely, fewer groups focused on their stabilization to obtain “stealth” allogenic EVs. Modulating their stabilization and biodistribution is an essential prerequisite for their development as nano-therapeutics. Here, we explored polyoxazolines with lipid anchors association to the EV membrane (POxylation as an alternative to PEGylation) to stabilize EVs in plasma and control their biodistribution, while preserving their native properties. We found that this modification maintained and seemed to potentiate the immunomodulatory properties of EVs derived from mesenchymal stem/stromal cells (MSC). Using a radiolabeling protocol to track EVs at a therapeutically relevant concentration in vivo, we demonstrated that POxylation is a promising option to stabilize EVs in plasma because it increased EV half-life by 6 fold at 6 h post-injection. Moreover, EV accumulation in tumors was higher after POxylation than after PEGylation.

Original languageEnglish
Article number122748
Number of pages19
JournalBiomaterials
Volume313
Early online date5 Aug 2024
DOIs
Publication statusPublished - Feb 2025

Keywords

  • 2024 OA procedure
  • EV radiolabeling
  • Exosomes
  • Lipopolymer
  • Lipopolyoxazoline
  • Pharmacokinetics
  • Post-insertion
  • biodistribution

Fingerprint

Dive into the research topics of 'Surface modification of extracellular vesicles with polyoxazolines to enhance their plasma stability and tumor accumulation'. Together they form a unique fingerprint.

Cite this