Posted by Here a new βCD-based nucleic acid delivery platform is proposed that surmounts the former archetype in its capacity to encode topological information. These vectors display cationic centers homogeneously distributed at both the primary O6 and the secondary O2 positions. The hydrophobic tails are then anchored at the seven O3 positions. Such distribution of functional elements frustrates the two-face sharp segregation of cationic and lipophilic domains characteristic of Janus MNPs. In the scientific literature, the term “frustrated amphiphiles” has been coined to refer to amphiphilic molecules for which the divergent alignment of the hydrophilic head and the lipid tail is hindered due to unfavorable hydrogen-bonding or electrostatic interactions. By analogy, we use here “geometrically frustrated amphiphiles” (GFAs) to refer to amphiphilic nanoparticles for which the typical opposite orientation of hydrophilic and lipophilic moieties is disfavored by architectural constrains.
The intriguing overlap of cell linages and tissue targets strongly suggests that receptor-mediated mechanisms, issued from preferential adsorption of distinct serum proteins on the particle surface, might operate to a certain extent. Nevertheless, the contribution of nanocomplex topology and protein corona composition to the in vitro and in vivo transfection mechanisms of GFA-based nanoparticles needs experimental validation, and it is essential to be cautious about making any generalizations.
Gonzalo Rivero-Barbarroja, José López-Fernández, Inmaculada Juárez-Gonzálvez, Carlos Fernández-Clavero, Christophe Di Giorgio, Itziar Vélaz, María J. Garrido, Juan M. Benito, Carmen Ortiz Mellet, Francisco Mendicuti, Conchita Tros de Ilarduya, José M. García Fernández (2025) β-Cyclodextrin-based geometrically frustrated amphiphiles as one-component, cell-specific and organ-specific nucleic acid delivery systems.
Carbohydrate Polymers 347, 122776. https://doi.org/10.1016/j.carbpol.2024.122776