Neutral high-generation phosphorus dendrimers inhibit macrophage-mediated inflammatory response in vitro and in vivo

Abstract

Inflammation is part of the physiological response of the organism to infectious diseases caused by organisms such as bacteria, viruses, fungi, or parasites. Innate immunity, mediated by mononuclear phagocytes, including monocytes and macrophages, is a first line of defense against infectious diseases and plays a key role triggering the delayed adaptive response that ensures an efficient defense against pathogens. Monocytes and macrophages stimulation by pathogen antigens results in activation of different signaling pathways leading to the release of proinflammatory cytokines. However, inflammation can also participate in the pathogenesis of several diseases, the autoimmune diseases that represent a relevant burden for human health. Dendrimers are branched, multivalent nanoparticles with a well-defined structure that have a high potential for biomedical applications. To explore new approaches to fight against the negative aspects of inflammation, we have used neutral high-generation phosphorus dendrimers bearing 48 (G3) or 96 (G4) bisphosphonate groups on their surface. These dendrimers show no toxicity and have good solubility and chemical stability in aqueous solutions. Here, we present data indicating that neutral phosphorus dendrimers show impressive antiinflammatory activities both in vitro and in vivo. In vitro, these dendrimers reduced the secretion of proinflammatory cytokines from mice and human monocytederived macrophages. In addition, these molecules present efficient antiinflammatory activity in vivo in a mouse model of subchronic inflammation. Taken together, these data suggest that neutral G3-G4 phosphorus dendrimers have strong potential applications in the therapy of inflammation and, likely, of autoimmune diseases.dendrimers | inflammation | innate immunity | air pouch | macrophage

In Search of a Phosphorus Dendrimer-Based Carrier of Rose Bengal: Tyramine Linker Limits Fluorescent and Phototoxic Properties of a Photosensitizer

“…It was shown that the G3–3RB–pyrro conjugate retained the nanometric size and significant surface positive charge ( Table 1 ), potentially favoring efficient endocytosis and cell entry [ 22 ]. However, when compared with our previous research [ 23 ], the size of the tested conjugate was enlarged, suggesting the possibility of aggregation.…”

Synergistic Effects of Anionic/Cationic Dendrimers and Levofloxacin on Antibacterial Activities

“…Because of many interesting properties, phosphorus dendrimers are of great interest for drug delivery applications, anti-prion, imaging [27], anti-cancer [28,29,30], and anti-inflammatory agents [31,32,33]. Moreover, polyanionic and polycationic phosphorus dendrimers have been proposed as carriers for photosensitizers in photodynamic therapy [34].…”

Nanoscience in Multiple Sclerosis

“…Dendrimers show high water solubility, stability, permeability of drug 39,40 , biocompatibility 41 , polyvalency 42 and precise molecular weights 43 , which makes them an ideal carrier for drug delivery. Various types of dendrimers such as polyamidoamine (PAMAM), poly(propylene imine) (PPI), poly-L-lysine, melamine, poly(etherhydroxylamine) (PEHAM), poly(esteramine) (PEA) and polyglycerol have been synthesized and studied as drug delivery vehicles 44,45 . Neutral G3-G4 phosphate dendrimers are recently explored for their ability to reduce secretion of proinflammatory cytokines from mice and human monocytederived macrophages 46 .…”