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Long-Acting Heterodimeric Paclitaxel-Idebenone Prodrug-Based Nanomedicine Promotes Functional Recovery after Spinal Cord Injury.
- Source :
-
Nano letters [Nano Lett] 2024 Mar 20; Vol. 24 (11), pp. 3548-3556. Date of Electronic Publication: 2024 Mar 08. - Publication Year :
- 2024
-
Abstract
- After spinal cord injury (SCI), successive systemic administration of microtubule-stabilizing agents has been shown to promote axon regeneration. However, this approach is limited by poor drug bioavailability, especially given the rapid restoration of the blood-spinal cord barrier. There is a pressing need for long-acting formulations of microtubule-stabilizing agents in treating SCI. Here, we conjugated the antioxidant idebenone with microtubule-stabilizing paclitaxel to create a heterodimeric paclitaxel-idebenone prodrug via an acid-activatable, self-immolative ketal linker and then fabricated it into chondroitin sulfate proteoglycan-binding nanomedicine, enabling drug retention within the spinal cord for at least 2 weeks and notable enhancement in hindlimb motor function and axon regeneration after a single intraspinal administration. Additional investigations uncovered that idebenone can suppress the activation of microglia and neuronal ferroptosis, thereby amplifying the therapeutic effect of paclitaxel. This prodrug-based nanomedicine simultaneously accomplishes neuroprotection and axon regeneration, offering a promising therapeutic strategy for SCI.
Details
- Language :
- English
- ISSN :
- 1530-6992
- Volume :
- 24
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Nano letters
- Publication Type :
- Academic Journal
- Accession number :
- 38457277
- Full Text :
- https://doi.org/10.1021/acs.nanolett.4c00856