posted on 2020-02-07, 18:33authored byFilip Stojceski, Gianvito Grasso, Lorenzo Pallante, Andrea Danani
Dendrimer
nanocarriers are unique hyper-branched polymers with
biomolecule-like properties, representing a promising prospect as
a nucleic acid delivery system. The design of effective dendrimer-based
gene carriers requires considering several parameters, such as carrier
morphology, size, molecular weight, surface chemistry, and flexibility/rigidity.
In detail, the rational design of the dendrimer surface chemistry
has been ascertained to play a crucial role on the efficiency of interaction
with nucleic acids. Within this framework, advances in the field of
organic chemistry have allowed us to design dendrimers with even small
difference in the chemical structure of their surface terminals. In
this study, we have selected two different cationic phosphorus dendrimers
of generation 3 functionalized, respectively, with pyrrolidinium (DP)
and morpholinium (DM) surface groups, which have demonstrated promising
potential for short interfering RNA (siRNA) delivery. Despite DP and
DM differing only for one atom in their chemical structure, in vitro
and in vivo experiments have highlighted several differences between
them in terms of siRNA complexation properties. In this context, we
have employed coarse-grained molecular dynamics simulation techniques
to shed light on the supramolecular characteristics of dendrimer–siRNA
complexation, the so-called dendriplex formations. Our data provide
important information on self-assembly dynamics driven by surface
chemistry and competition mechanisms.