Trifaceted Mickey Mouse Amphiphiles for Programmable Self-Assembly, DNA Complexation and Organ-Selective Gene Delivery

Autor: José L. Jiménez Blanco, Conchita Tros de Ilarduya, Christophe Di Giorgio, José M. García Fernández, Juan M. Benito, Carmen Ortiz Mellet, Manuel González-Cuesta, Cédric Przybylski, María L. Santana-Armas, Thais Carmona, Francisco Mendicuti, Ana I. Carbajo-Gordillo
Přispěvatelé: Universidad de Sevilla. Departamento de Química orgánica, Ministerio de Ciencia, Innovación y Universidades (MICINN). España, Agencia Estatal de Investigación. España, Universidad de Alcalá de Henares, European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Universidad de Sevilla, Universidad Pública de Navarra [Espagne] = Public University of Navarra (UPNA), Universidad de Alcalá - University of Alcalá (UAH), Institut de Chimie de Nice (ICN), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Institut Parisien de Chimie Moléculaire (IPCM), Chimie Moléculaire de Paris Centre (FR 2769), Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Chemistry (Weinheim an Der Bergstrasse, Germany)
Chemistry-A European Journal
Chemistry-A European Journal, Wiley-VCH Verlag, 2021, 27 (36), pp.9429-9438. ⟨10.1002/chem.202100832⟩
Digital.CSIC. Repositorio Institucional del CSIC
instname
idUS. Depósito de Investigación de la Universidad de Sevilla
Digital.CSIC: Repositorio Institucional del CSIC
Consejo Superior de Investigaciones Científicas (CSIC)
ISSN: 0947-6539
1521-3765
Popis: Instilling segregated cationic and lipophilic domains with an angular disposition in a trehalose‐based trifaceted macrocyclic scaffold allows engineering patchy molecular nanoparticles leveraging directional interactions that emulate those controlling self‐assembling processes in viral capsids. The resulting trilobular amphiphilic derivatives, featuring a Mickey Mouse architecture, can electrostatically interact with plasmid DNA (pDNA) and further engage in hydrophobic contacts to promote condensation into transfectious nanocomplexes. Notably, the topology and internal structure of the cyclooligosaccharide/pDNA co‐assemblies can be molded by fine‐tuning the valency and characteristics of the cationic and lipophilic patches, which strongly impacts the transfection efficacy in vitro and in vivo. Outstanding organ selectivities can then be programmed with no need of incorporating a biorecognizable motif in the formulation. The results provide a versatile strategy for the construction of fully synthetic and perfectly monodisperse nonviral gene delivery systems uniquely suited for optimization schemes by making cyclooligosaccharide patchiness the focus.
Mickey Mouse molecular nanoparticles with a trehalose‐based cyclooligosaccharide core and uneven distributions of cationic (C, red lobules) and lipophilic patches (L, blue lobules) co‐assemble with plasmid DNA (pDNA, orange chains) to afford transfectious nanacomplexes with programmable topologies and internal structures, ranging from multilamellar spheroids and rods to core‐shell arrangements, translating into amazing cell efficiencies in vitro and organ selectivities in vivo with no need of targeting labels.
Databáze: OpenAIRE
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