Enhanced Gene Delivery Triggered by Dual pH/Redox Responsive Host‐Guest Dimerization of Cyclooligosaccharide Star Polycations - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Macromolecular Rapid Communications Année : 2022

Enhanced Gene Delivery Triggered by Dual pH/Redox Responsive Host‐Guest Dimerization of Cyclooligosaccharide Star Polycations

Ana Carbajo-Gordillo
José López-Fernández
  • Fonction : Auteur
Juan Benito
José Jiménez Blanco
María Santana-Armas
  • Fonction : Auteur
Gema Marcelo
  • Fonction : Auteur
Christophe Di Giorgio
Carmen Ortiz Mellet
Conchita Tros de Ilarduya
  • Fonction : Auteur
Francisco Mendicuti
  • Fonction : Auteur
José García Fernández

Résumé

A robust strategy is reported to build perfectly monodisperse star polycations combining a trehalose-based cyclooligosaccharide (cyclotrehalan, CT) central core onto which oligoethyleneimine radial arms are installed. The architectural perfection of the compounds is demonstrated by a variety of physicochemical techniques, including NMR, MS, DLS, TEM, and GPC. Key to the strategy is the possibility of customizing the cavity size of the macrocyclic platform to enable/prevent the inclusion of adamantane motifs. These properties can be taken into advantage to implement sequential levels of stimuli responsiveness by combining computational design, precision chemistry and programmed host-guest interactions. Specifically, it is shown that supramolecular dimers implying a trimeric CT-tetraethyleneimine star polycation and purposely designed bis-adamantane guests are preorganized to efficiently complex plasmid DNA (pDNA) into transfection-competent nanocomplexes. The stability of the dimer species is responsive to the protonation state of the cationic clusters, resulting in dissociation at acidic pH. This process facilitates endosomal escape, but reassembling can take place in the cytosol then handicapping pDNA nuclear import. By equipping the ditopic guest with a redox-sensitive disulfide group, recapturing phenomena are prevented, resulting in drastically improved transfection efficiencies both in vivo and in vitro.

Domaines

Chimie

Dates et versions

hal-04049810 , version 1 (28-03-2023)

Identifiants

Citer

Ana Carbajo-Gordillo, José López-Fernández, Juan Benito, José Jiménez Blanco, María Santana-Armas, et al.. Enhanced Gene Delivery Triggered by Dual pH/Redox Responsive Host‐Guest Dimerization of Cyclooligosaccharide Star Polycations. Macromolecular Rapid Communications, 2022, 43 (11), pp.2200145. ⟨10.1002/marc.202200145⟩. ⟨hal-04049810⟩
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