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Arsonium‐Containing Lipophosphoramides, Poly‐Functional Nano‐Carriers for Simultaneous Antibacterial Action and Eukaryotic Cell Transfection
Author(s) -
Le Gall Tony,
Berchel Mathieu,
Le Hir Sophie,
Fraix Aurore,
Salaün Jean Yves,
Férec Claude,
Lehn Pierre,
Jaffrès PaulAlain,
Montier Tristan
Publication year - 2013
Publication title -
advanced healthcare materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.288
H-Index - 90
eISSN - 2192-2659
pISSN - 2192-2640
DOI - 10.1002/adhm.201200478
Subject(s) - transfection , bacteria , amphiphile , cationic polymerization , in vivo , genetic enhancement , biofilm , gene delivery , in vitro , gene transfer , cystic fibrosis , chemistry , microbiology and biotechnology , cell , gene , secretion , biology , biochemistry , polymer , organic chemistry , genetics , copolymer
Abstract Gene therapy of diseases like cystic fibrosis (CF) would consist of delivering a gene medicine towards the lungs via the respiratory tract into the target epithelial cells. Accordingly, poly‐functional nano‐carriers are required in order to overcome the various successive barriers of such a complex environment, such as airway colonization with bacterial strains. In this work, the antibacterial effectiveness of a series of cationic lipids is investigated before evaluating its compatibility with gene transfer into human bronchial epithelial cells. Among the various compounds considered, some bearing a trimethyl‐arsonium headgroup demonstrate very potent biocide effects towards clinically relevant bacterial strains. In contrast to cationic lipids exhibiting no or insufficient antibacterial potency, arsonium‐containing lipophosphoramides can simultaneously inhibit bacteria while delivering DNA into eukaryotic cells, as efficiently and safely as in absence of bacteria. Moreover, such vectors can demonstrate antibacterial activity in vitro while retaining high gene transfection efficiency to the nasal epithelium as well as to the lungs in mice in vivo. Arsonium‐containing amphiphiles are the first synthetic compounds shown to achieve efficient gene delivery in the presence of bacteria, a property particularly suitable for gene therapy strategies under infected conditions such as within the airways of CF patients.