Issue 14, 2024

Trehalose-polyamine/DNA nanocomplexes: impact of vector architecture on cell and organ transfection selectivity

Abstract

A novel family of precision-engineered gene vectors with well-defined structures built on trehalose and trehalose-based macrocycles (cyclotrehalans) comprising linear or cyclic polyamine heads have been synthesized through procedures that exploit click chemistry reactions. The strategy was conceived to enable systematic structural variations and, at the same time, ensuring that enantiomerically pure vectors are obtained. Notably, changes in the molecular architecture translated into topological differences at the nanoscale upon co-assembly with plasmid DNA, especially regarding the presence of regions with short- or long-range internal order as observed by TEM. In vitro and in vivo experiments further evidenced a significant impact on cell and organ transfection selectivity. Altogether, the results highlight the potential of trehalose-polyamine/pDNA nanocomplex monoformulations to achieve targeting transfection without the need for any additional cell- or organ-sorting component.

Graphical abstract: Trehalose-polyamine/DNA nanocomplexes: impact of vector architecture on cell and organ transfection selectivity

Supplementary files

Article information

Article type
Paper
Submitted
07 Dec 2023
Accepted
05 Mar 2024
First published
05 Mar 2024
This article is Open Access
Creative Commons BY license

J. Mater. Chem. B, 2024,12, 3445-3452

Trehalose-polyamine/DNA nanocomplexes: impact of vector architecture on cell and organ transfection selectivity

F. Ortega-Caballero, M. L. Santana-Armas, C. Tros de Ilarduya, C. Di Giorgio, R. Tripier, N. Le Bris, C. Ollier, C. Ortiz Mellet, J. M. García Fernández, J. L. Jiménez Blanco and A. Méndez-Ardoy, J. Mater. Chem. B, 2024, 12, 3445 DOI: 10.1039/D3TB02889E

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