Dépôt numérique

Deep Tissue Penetration of Bottle-Brush Polymers via Cell Capture Evasion and Fast Diffusion

Rabanel, Jean-Michel; Mirbagheri, Marziye; Olszewski, Mateusz; Xie, Guojun; Le Goas, Marine; Latreille, Pierre-Luc; Counil, Hermine; Hervé, Vincent; Silva, Rummenigge Oliveira; Zaouter, Charlotte; Adibnia, Vahid; Acevedo, Mariana; Servant, Marc J; Martinez, Vincent A; Patten, Shunmoogum A. ORCID logoORCID: https://orcid.org/0000-0002-2782-3547; Matyjaszewski, Krzysztof; Ramassamy, Charles ORCID logoORCID: https://orcid.org/0000-0002-3252-5878 et Banquy, Xavier (2022). Deep Tissue Penetration of Bottle-Brush Polymers via Cell Capture Evasion and Fast Diffusion ACS Nano , vol. 16 . pp. 21583-21599. DOI: 10.1021/acsnano.2c10554.

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Drug nanocarriers (NCs) capable of crossing the vascular endothelium and deeply penetrating into dense tissues of the CNS could potentially transform the management of neurological diseases. In the present study, we investigated the interaction of bottle-brush (BB) polymers with different biological barriers in vitro and in vivo and compared it to nanospheres of similar composition. In vitro internalization and permeability assays revealed that BB polymers are not internalized by brain-associated cell lines and translocate much faster across a blood-brain barrier model compared to nanospheres of similar hydrodynamic diameter. These observations performed under static, no-flow conditions were complemented by dynamic assays performed in microvessel arrays on chip and confirmed that BB polymers can escape the vasculature compartment via a paracellular route. BB polymers injected in mice and zebrafish larvae exhibit higher penetration in brain tissues and faster extravasation of microvessels located in the brain compared to nanospheres of similar sizes. The superior diffusivity of BBs in extracellular matrix-like gels combined with their ability to efficiently cross endothelial barriers via a paracellular route position them as promising drug carriers to translocate across the blood-brain barrier and penetrate dense tissue such as the brain, two unmet challenges and ultimate frontiers in nanomedicine.

Type de document: Article
Mots-clés libres: blood-brain barrier; bottle-brush polymer; mouse; vessel-on-a-chip; zebrafish.
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 11 déc. 2023 14:23
Dernière modification: 11 déc. 2023 14:23
URI: https://espace.inrs.ca/id/eprint/13456

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