Avoiding undesired effects in the interaction of nanostructures with immune cells: the Role of Oxyresveratrol

Poly(lactic-co-glycolic acid) (PLGA) nanoparticles are considered as biocompatible both by the U.S.Food and Drug Administration (FDA) and the European Medicines Agency (EMA)1. Nevertheless, such nanomaterials could cause some undesired effects due to unexpected “cell priming”. The interaction of nanostructures with the immune cells could lead to unexpected effects, especially if microorganisms are present in the tissues of patients to whom nanoparticles are administered. In this scenario, we observed an increase in the secretion of IL-12, IL-6 and TNF-α in Dendritic Cells stimulated with R848, an event known as the “priming effect”, once PLGA NPs were administrated2. We also assessed that bare nanoparticles induce O2− production by resting monocytes and enhance the formation of this radical in β-glucan-stimulated monocytes3. Dendritic cells are involved in modulating the adaptive immune reaction and the inflammatory process to combat pathogenic microorganisms, while monocytes are heterogeneous cells circulating in the blood that initiate and propagate the immune response by phagocytosing pathogens and releasing chemical mediators. Oxyresveratrol is a polyphenol extracted from Artocarpus lakoocha Roxb. heartwood, a plant known in Thailand as ‘Ma-Haad’ and used in traditional medicine. The anti-inflammatory effect of oxyresveratrol is mainly attributed to downregulation of pro-inflammatory cytokine production4; it has also been reported as a good antioxidant, equipped with ROS scavenger activity5. Moreover, compared to resveratrol, the additional OH- group should increase the biological effect. We investigated if the anti-inflammatory and the ROS scavenging activity of oxyresveratrol, were able to mitigate the pro-inflammation and ROS production upon nanoparticles interaction with both Dendritic and Monocytes cells, once it was incorporate into PLGA Nanoparticles. Our finding suggests not only that the polyphenol reduce the O2− during the cellular uptake of both resting and β-glucan-stimulated Monocytes but, it can also contrast the unwanted release of pro-inflammatory cytokines by Dendritic Cells, due to a synergistic effect of nanoparticles with microbial agents that could be present in the patient tissues2,3.On the one hand the encapsulation of the polyphenol in PLGA increases its effectiveness and bioavailability and oxyresveratrol mitigates any dangerous effect especially if the nanoparticles are administered to patients with an overstressed immune system.