Pro-Inflammatory Versus Anti-Inflammatory Effects of Dendrimers: The Two Faces of Immuno-Modulatory Nanoparticles

Abstract

Dendrimers are soft matter, hyperbranched, and multivalent nanoparticles whose synthesis theoretically affords monodisperse compounds. They are built from a core on which one or several successive series of branches are engrafted in an arborescent way. At the end of the synthesis, the tunable addition of surface groups gives birth to multivalent nano-objects which are generally intended for a specific use. For these reasons, dendrimers have received a lot of attention from biomedical researchers. In particular, some of us have demonstrated that dendrimers can be intrinsically drug-candidate for the treatment of inflammatory disorders, amongst others, using relevant preclinical animal models. These anti-inflammatory dendrimers are innovative in the pharmaceutical field. More recently, it has appeared that some dendrimers (even among those which have been described as anti-inflammatory) can promote inflammatory responses in non-diseased animals. The main corpus of this concise review is focused on the reports which describe anti-inflammatory properties of dendrimers in vivo, following which we review the few recent articles that show pro-inflammatory effects of our favorite molecules, to finally discuss this duality in immuno-modulation which has to be taken into account for the preclinical and clinical developments of dendrimers.

Keywords: dendrimers; immuno-safety; inflammation; nanoparticles.

Figure 1

Schematic synthesis of a generation 2 (two series of branches) dendrimer using a tetravalent core (i.e., four branches in the first series) and trivalent points of divergence (i.e., 12 branches in the second series, and 36 surface groups). r1 and r2 are the reactions which are iterated to obtain the final dendrimer.