Synthesis of pH-Cleavable dPG-Amines for Gene Delivery Application

Mathias Dimde, Dirk Steinhilber, Falko Neumann, Yan Li, Florian Paulus, Nan Ma, and Rainer Haag – 2017

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 benz­acetal 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.

Titel
Synthesis of pH-Cleavable dPG-Amines for Gene Delivery Application
Verfasser
Mathias Dimde, Dirk Steinhilber, Falko Neumann, Yan Li, Florian Paulus, Nan Ma, and Rainer Haag
Datum
2017
Kennung
10.1002/mabi.201600190
Zitierweise
Macromol. Biosci. 2017, 17, 1600190
Art
Text
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