Development of simplified poly(β-aminoester)-zwitterion nanovehicles for transfection of cancer cells and improved gene delivery across a cell-based model of the blood-brain barrier
Although nucleotide-based therapeutics hold promise for a variety of diseases, their clinical application is limited because of low stability and poor bioavailability. Among non-viral gene delivery vectors, poly(β-aminoester)s (pBAEs) stand out because of their low cytotoxicity, high transfection ca...
| Autores: | , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2025 |
| País: | España |
| Institución: | Universitat Ramon Llull (URL) |
| Repositorio: | DAU Arxiu Digital de la Universitat Ramon Llull |
| OAI Identifier: | oai:dau.url.edu:20.500.14342/5506 |
| Acceso en línea: | http://hdl.handle.net/20.500.14342/5506 https://doi.org/10.1007/s13346-025-01902-z |
| Access Level: | acceso embargado |
| Palabra clave: | OM-pBAE nanoparticles Targeted gene delivery Zwitterionic peptides Brain shuttle peptides Nanopartícules Pèptids Cervell Cancer cells Cèl·lules canceroses 577 |
| Sumario: | Although nucleotide-based therapeutics hold promise for a variety of diseases, their clinical application is limited because of low stability and poor bioavailability. Among non-viral gene delivery vectors, poly(β-aminoester)s (pBAEs) stand out because of their low cytotoxicity, high transfection capacity, and adequate biodegradation profile. Oligopeptide end-Modified pBAEs (OM-pBAEs) enable enhanced polynucleotide encapsulation, cellular internalization, and transfection. Despite the outstanding properties of OM-pBAEs as non-viral gene delivery vectors, traditional OM-pBAE formulations have low cell selectivity and require formulation with two or more polymers. In this study, we first develop a simplified OM-pBAE formulation with a single polymer (pBAE-CRHR) and then add a zwitterionic moiety as part of the end-capping process (pBAE-CRHR-Zw) to decrease unspecific transfection. Subsequently, we recover transfection capacity for target cancer cells in two ways: (i) by addition of a photo-cleavable moiety between the pBAE and the zwitterion, and (ii) by functionalization of pBAEs with BrainBike-4, a bicyclic peptidomimetic targeting the transferrin receptor 1. Finally, we show that derivatization of pBAE-CRHR-Zw with BrainBike-4 enhances transmigration of the gene delivery system across a tight monolayer of human endothelial cells mimicking the BBB. |
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