The key role of the scaffold on the efficiency of dendrimer nanodrugs

Abstract

Dendrimers are well-defined macromolecules whose highly branched structure is reminiscent of many natural structures, such as trees, dendritic cells, neurons or the networks of kidneys and lungs. Nature has privileged such branched structures for increasing the efficiency of exchanges with the external medium; thus, the whole structure is of pivotal importance for these natural networks. On the contrary, it is generally believed that the properties of dendrimers are essentially related to their terminal groups, and that the internal structure plays the minor role of an ‘innocent' scaffold. Here we show that such an assertion is misleading, using convergent information from biological data (human monocytes activation) and all-atom molecular dynamics simulations on seven families of dendrimers (13 compounds) that we have synthesized, possessing identical terminal groups, but different internal structures. This work demonstrates that the scaffold of nanodrugs strongly influences their properties, somewhat reminiscent of the backbone of proteins.

Recent therapeutic applications of the theranostic principle with dendrimers in oncology

“…19) was used to decipher the biological processes leading to the anticancer properties. It was shown that the first step is the anti-inflammatory activation of monocytes, which is particularly important against chronic inflammatory diseases [83,84]. In second time, a cross-talk between monocytes and NK cells induces the proliferation of the latter, including with blood from patients suffering of multiple myeloma disease [85].…”

Low generation polyamine dendrimers bearing flexible tetraethylene glycol as nanocarriers for plasmids and siRNA

“…Indeed, as shown in Fig. 5, molecular modeling of one of the relaxed conformers of dendrimer 5 (G1-30 NH 2 ), wherein two of the amine pairs can span over a distance of 52 Å may account for the dendrimer's conformational adaptation 62 to better reach the anionic phosphate groups on plasmid DNA and siRNA. The above data confirm that polycationic pegylated dendrimers of low generation (G1 here) hold great promise as nanocarriers for gene transfection.…”

PAMAM dendrimer based targeted nano-carrier for bio-imaging and therapeutic agents

“…25,34 The starburst PAMAM dendrimers used today have an ethylenediamine core based on the reports of Tomalia et al 16 25,34 The starburst PAMAM dendrimers used today have an ethylenediamine core based on the reports of Tomalia et al 16 …”