Article Dans Une Revue Nature Nanotechnology Année : 2014

Squalenoyl adenosine nanoparticles provide neuroprotection after stroke and spinal cord injury

Niko Hildebrandt
Julie Mougin
Sabrina Valetti
Didier Desmaële
Karine Andrieux
Yilmaz Capan
  • Fonction : Auteur
Patrick Couvreur

Résumé

There is an urgent need to develop new therapeutic approaches for the treatment of severe neurological trauma, such as stroke and spinal cord injuries. However, many drugs with potential neuropharmacological activity, such as adenosine, are inefficient upon systemic administration because of their fast metabolization and rapid clearance from the bloodstream. Here, we show that conjugation of adenosine to the lipid squalene and the subsequent formation of nanoassemblies allows prolonged circulation of this nucleoside, providing neuroprotection in mouse stroke and rat spinal cord injury models. The animals receiving systemic administration of squalenoyl adenosine nanoassemblies showed a significant improvement of their neurologic deficit score in the case of cerebral ischaemia, and an early motor recovery of the hindlimbs in the case of spinal cord injury. Moreover, in vitro and in vivo studies demonstrated that the nanoassemblies were able to extend adenosine circulation and its interaction with the neurovascular unit. This Article shows, for the first time, that a hydrophilic and rapidly metabolized molecule such as adenosine may become pharmacologically efficient owing to a single conjugation with the lipid squalene.

Dates et versions

hal-04119812 , version 1 (06-06-2023)

Identifiants

Citer

Alice Gaudin, Müge Yemisci, Hakan Eroglu, Sinda Lepetre-Mouelhi, Omer Faruk Turkoglu, et al.. Squalenoyl adenosine nanoparticles provide neuroprotection after stroke and spinal cord injury. Nature Nanotechnology, 2014, 9 (12), pp.1054-1062. ⟨10.1038/nnano.2014.274⟩. ⟨hal-04119812⟩
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