Cross-linked polymers with fluorinated bridges for efficient gene delivery

A new strategy for the construction of fluorinated cationic polymers for gene delivery was introduced. The fluorinated polymers were synthesized by crosslinking low molecular weight PEI with diols containing various lengths of perfluoroalkyl chains via epoxide ring-opening polymerization. Such a study presents the first example of polymeric gene vectors with fluorination on the polymer backbone but not on the side chains. These materials showed good DNA condensation and protection ability and could condense DNA into nanoparticles with appropriate sizes and zeta-potentials. The fluorine atoms might strengthen the interaction toward DNA, leading to more stable polyplexes. In vitro transfection results showed that the fluorinated polymers could mediate efficient gene delivery toward both 2D and 3D cell cultures at low weight ratios, and their transfection efficiency was higher than that of PEI 25 kDa and their non-fluorinated counterparts. Several assays including DLS, TEM, luciferase reporter gene transfection and flow cytometry revealed that fluorination improved the serum resistance of these polymeric vectors, and more fluorine atoms might lead to better serum tolerance. These fluorinated materials exhibited very low cytotoxicity at transfection dosage. A cellular uptake study with uptake inhibitors indicated that macro-pinocytosis and microtubule-mediated endocytosis were the major endocytosis pathways for these polyplexes.

Medienart:

E-Artikel

Erscheinungsjahr:

2017

Erschienen:

2017

Enthalten in:

Zur Gesamtaufnahme - volume:5

Enthalten in:

Journal of materials chemistry. B - 5(2017), 43 vom: 21. Nov., Seite 8542-8553

Sprache:

Englisch

Beteiligte Personen:

Xiao, Ya-Ping [VerfasserIn]
Zhang, Ji [VerfasserIn]
Liu, Yan-Hong [VerfasserIn]
Huang, Zheng [VerfasserIn]
Wang, Bing [VerfasserIn]
Zhang, Yi-Mei [VerfasserIn]
Yu, Xiao-Qi [VerfasserIn]

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Date Revised 08.04.2020

published: Print-Electronic

Citation Status PubMed-not-MEDLINE

doi:

10.1039/c7tb02158e

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM30849802X