β-Cyclodextrin-based geometrically frustrated amphiphiles as one-component, cell-specific and organ-specific nucleic acid delivery systems.

Autor: Rivero-Barbarroja G; Department of Organic Chemistry, Faculty of Chemistry, University of Seville, 41012 Sevilla, Spain., López-Fernández J; Instituto de Investigaciones Químicas (IIQ), CSIC - Universidad de Sevilla, 41092 Sevilla, Spain., Juárez-Gonzálvez I; Department of Pharmaceutical Sciences, School of Pharmacy and Nutrition, University of Navarra, 31080 Pamplona, Spain., Fernández-Clavero C; Departamento de Química Analítica, Química Física e Ingeniería Química and Instituto de Investigación Química 'Andrés del Rio', Universidad de Alcalá, Spain., Di Giorgio C; Institut de Chimie Nice, UMR 7272, Université Côte d'Azur, F-06108 Nice, France., Vélaz I; Department of Chemistry, School of Sciences, University of Navarra, 31080 Pamplona, Spain., Garrido MJ; Department of Pharmaceutical Sciences, School of Pharmacy and Nutrition, University of Navarra, 31080 Pamplona, Spain., Benito JM; Instituto de Investigaciones Químicas (IIQ), CSIC - Universidad de Sevilla, 41092 Sevilla, Spain., Ortiz Mellet C; Department of Organic Chemistry, Faculty of Chemistry, University of Seville, 41012 Sevilla, Spain. Electronic address: mellet@us.es., Mendicuti F; Departamento de Química Analítica, Química Física e Ingeniería Química and Instituto de Investigación Química 'Andrés del Rio', Universidad de Alcalá, Spain. Electronic address: francisco.mendicuti@uah.es., Tros de Ilarduya C; Department of Pharmaceutical Sciences, School of Pharmacy and Nutrition, University of Navarra, 31080 Pamplona, Spain. Electronic address: ctros@unav.es., García Fernández JM; Instituto de Investigaciones Químicas (IIQ), CSIC - Universidad de Sevilla, 41092 Sevilla, Spain. Electronic address: jogarcia@iiq.csic.es.
Jazyk: angličtina
Zdroj: Carbohydrate polymers [Carbohydr Polym] 2025 Jan 01; Vol. 347, pp. 122776. Date of Electronic Publication: 2024 Sep 24.
DOI: 10.1016/j.carbpol.2024.122776
Abstrakt: We introduce an innovative β-cyclodextrin (βCD)-prototype for delivering nucleic acids: "geometrically frustrated amphiphiles (GFAs)." GFAs are designed with cationic centers evenly distributed across the primary O6 and secondary O2 positions of the βCD scaffold, while hydrophobic tails are anchored at the seven O3 positions. Such distribution of functional elements differs from Janus-type architectures and enlarges the capacity for accessing strictly monodisperse variants. Changes at the molecular level can then be correlated with preferred self-assembly and plasmid DNA (pDNA) co-assembly behaviors. Specifically, GFAs undergo pH-dependent transition between bilayered to monolayered vesicles or individual molecules. GFA-pDNA nanocomplexes exhibit topological and internal order characteristics that are also a function of the GFA molecular architecture. Notably, adjusting the pK a of the cationic heads and the hydrophilic-hydrophobic balance, pupa-like arrangements implying axial alignments of GFA units flanked by quasi-parallel pDNA segments are preferred. In vitro cell transfection studies revealed remarkable differences in relative performances, which corresponded to distinct organ targeting outcomes in vivo. This allowed for preferential delivery to the liver and lung, kidney or spleen. The results collectively highlight cyclodextrin-based GFAs as a promising class of molecular vectors capable of finely tuning cell and organ transfection selectivity.
Competing Interests: Declaration of competing interest The authors declare no competing financial interest.
(Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: