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 monocyte-derived 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.
Subject(s)
Dendrimers/metabolism , Inflammation/metabolism , Animals , Anti-Inflammatory Agents/metabolism , Cell Culture Techniques , Cytokines/metabolism , Dendrimers/chemistry , Dendrimers/pharmacology , Humans , Immunity, Innate/drug effects , Inflammation/chemically induced , Lipopolysaccharides , Macrophages/metabolism , Mice , Mice, Inbred C57BL , Monocytes/metabolism , Nanoparticles/therapeutic use , Phosphorus/metabolismABSTRACT
Metallodrugs (organometallic complexes) bearing at least one metal-carbon bond - represent original and powerful tools for diverse therapeutic applications based on the development of "bioorganometallic chemistry". To date, various metallodrugs were described with very interesting biological activities as antimalarials, antibacterials, neuroprotectors, against arthritis, for chemotherapy etc. Anticancer Pt-based drugs are the main complexes used in the treatment of several cancers, but unfortunately these complexes show elicit and severe toxicities and resistance effects. The remarkably unique and tunable properties of dendrimers have made them promising tools for diverse biomedical applications such as diagnostics, gene therapy and drug delivery including in oncology. Recent studies have shown that well designed dendritic carriers overcome such as poor solubility, permeability, biocompatibility, bioavailability and toxicity of the native drug. This review reports on the recent advances for the use of metallodrugs and dendritic based carriers (drug-dendrimer conjugates and drug encapsulation) in oncology. Advantages, limitations and opportunities in oncology of such materials are discussed and compared.
