title: Synthesis of pH-Cleavable dPG-Amines for Gene Delivery Application.
abstract: The development of effective nonviral vectors for gene therapy is still a challenge in research, due to the high toxicity of many existing polycationic nanocarriers. In this paper, the development of two pH-cleavable polyglycerol-amine-based nanocarriers is described. The benz-acetal bond represents the pH-sensitive cleavage site between dendritic polyglycerol (dPG) and glycerol-based 1,2-diamines that can complex genetic material. Due to the acid lability of the acetal moiety, the cleavable dPG-amines are less toxic in vitro. Cell-mediated degradation results in non-toxic dPG with low amine functionalization and low molecular weight cleavage products (cp). The genetic material is released because of the loss of multivalent amine groups. Interestingly, the release kinetics at the endosomal pH could be controlled by simple chemical modification of the acetals. In vitro experiments demonstrate the ability of the cleavable dPG-amine to transfect HeLa cells with GFP-DNA, which resulted in cell-compatible cleavage products.
authors.affiliation: Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustrasse 3, Berlin, 14195, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Dimde
authors.affiliation: Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustrasse 3, Berlin, 14195, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Steinhilber
authors.affiliation: Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustrasse 3, Berlin, 14195, Germany.
authors.forename: Falko
authors.initials: F
authors.lastname: Neumann
authors.affiliation: Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustrasse 3, Berlin, 14195, Germany.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustrasse 3, Berlin, 14195, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Paulus
authors.affiliation: Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustrasse 3, Berlin, 14195, Germany.|Institute of Biomaterial Science and Berlin-Brandenburg Center for Regenerative Therapies Helmholtz-Zentrum Geesthacht, Kantstrasse 55, Teltow, 14513, Germany.
authors.forename: Nan
authors.initials: N
authors.lastname: Ma
authors.affiliation: Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustrasse 3, Berlin, 14195, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Haag
mesh_terms: D000588:Amines / Q000138:chemical synthesis* / Q000737:chemistry; D002470:Cell Survival; D050091:Dendrimers / Q000737:chemistry*; D000067493:Dynamic Light Scattering; D024202:Electrophoretic Mobility Shift Assay; D005453:Fluorescence; D018014:Gene Transfer Techniques; D005990:Glycerol / Q000737:chemistry*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D011108:Polymers / Q000737:chemistry*; D066244:Proton Magnetic Resonance Spectroscopy; D055672:Static Electricity; D014162:Transfection
chemical_list: D000588:Amines; D050091:Dendrimers; D011108:Polymers; D049452:Green Fluorescent Proteins; C043941:polyglycerol; D005990:Glycerol
keywords: DNA delivery; dendritic polyglycerol amines; gene transfection; pH cleavable