Abstract
The ability of certain triterpenoid saponins to modulate the endosomal release during
the process of endocytosis and to ensure a nontoxic and efficient transfection recently
led to an exceptional interest in the field of nonviral gene delivery. In vitro and in vivo studies demonstrated promising results in terms of tumor growth inhibition after
the delivery of a suicide gene such as saporin and dianthin. With that, the question
arises which structural features are necessary or advantageous to achieve an effective
endosomal escape. Former studies described certain important characteristics a potent
saponin should have. Particularly SA1641 (Gypsophila paniculata) and SO1861 (Saponaria officinalis) played an utmost important role to get a first insight into the structure-activity
relationship. However, a number of issues such as the purpose of functional groups
on the aglycon and the substitution of sugars and their modification remain unsolved
and their value needs to be specified. By conducting a screening of several diverse
saponins in terms of their transfection improving ability, we aimed to examine these
questions in more detail and get a better understanding of the relevant features.
The transfection of Neuro-2A-cells with GFP-DNA containing peptide-based nanoplexes
provided a reliable method in order to compare the activity of the saponins. With
that, we were able to provide new and essential insights regarding the structure-activity
relationship of transfection-modulating saponins and give an idea of how a highly
potent saponin for future gene therapies may look like.
Key words
triterpenoids - saponins - sapofection -
Gypsophila elegans
-
Saponaria officinalis
- Caryophyllaceae
