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• W4378953313 abstract "Retinal ganglion cell (RGC) neurodegeneration in glaucoma is not prevented by controlling the elevated intraocular pressure alone. Neuroprotective gene therapy approaches could be an essential part of a combination treatment. Five cell adhesion peptide (CAP)-gemini surfactants (18-7N(p1–5)-18) were synthesized as building blocks for brain-derived neurotrophic factor (BDNF) gene carrier nanoparticles (CAP-NPXs). The composition of CAP-NPXs was optimized, physicochemically characterized and evaluated for in vitro transfection efficiency (TE) in A7 astrocytes, 3D retinal neurospheres and for gene expression in vivo in CD1 mice using RFP reporter gene and BDNF levels after intravitreal (IVT) injection. The IgSF-binding 18-7N(pFASNKL)-18 pNPXs treated cells demonstrated 1.4-fold higher TE compared to integrin-binding 18-7N(pRGD)-18 pNPXs and parent 18-7NH-18 NPXs with overall viability between 86 and 95%. The 18-7N(pFASNKL)-18 pNPXs selectively transfected RGCs in 3D MiEye8 neurospheres. In the in vivo CD1 mouse model 18-7N(pFASNKL)-18 pNPXs administered by IVT injection delivered tdTomato/BDNF plasmid to retinal cells and produced higher gene expression than the 18-7N(pRGD)-18 pNPXs, the parent 18-7NH-18 NPXs and Lipofectamine® 3000 as demonstrated by confocal microscopy of whole mount retinas. The BDNF gene expression, assessed by ELISA, showed significantly high levels of BDNF with 18-7N(pFASNKL)-18 (422.60 ± 42.60 pg/eye), followed by 18-7N(pRGD)-18 pNPXs (230.62 ± 24.47 pg/eye), 18-7NH-18 NPXs (245.90 ± 39.72 pg/eye), Lipofectamine® 3000 (199.99 ± 29.90 pg/eye) and untreated controls (131.33 ± 20.30 pg/eye). In summary, the 18-7N(pFASNKL)-18 pNPXs induced 3.4-fold higher BDNF level compared to controls and 2-fold higher than 18-7N(pRGD)-18 pNPXs. The in vivo efficacy of 18-7N(pFASNKL)-18 NPXs to produce BDNF at pharmacologically relevant levels supports further studies." @default.
• W4378953313 created "2023-06-02" @default.
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• W4378953313 date "2023-07-01" @default.
• W4378953313 modified "2023-10-18" @default.
• W4378953313 title "BDNF gene delivery to the retina by cell adhesion peptide-conjugated gemini nanoplexes in vivo" @default.
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• W4378953313 doi "https://doi.org/10.1016/j.jconrel.2023.05.033" @default.
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