Different types of water-soluble phosphorous
dendrimers have been synthesized and display many different biological properties. It has been shown in particular that phosphorous
dendrimers of first generation functionalized with azabisphosphonate terminal functions are able to stimulate the human immune system ex vivo. These
dendrimers are internalized by monocytes within a few seconds, and induce their anti-inflammatory activation. The presence of the
dendrimers induces also the inhibition of the differentiation of monocytes into osteoclasts, the maturation of dendritic cells, and inhibits the proliferation of the proinflammatory CD4+ T lymphocytes. Finally, after 2-3 weeks of culture of peripheral blood mononuclear cells, amplifications by several
tens of natural killer cells is observed. In view of all these properties, the influence of these azabisphosphonate-
dendrimers has been tested in vivo with several animal models, against different chronic or acute inflammatory diseases, such as
multiple sclerosis,
rheumatoid arthritis,
uveitis, and
psoriasis, but also against
myeloid leukemia, a hematological
cancer. The hematological safety has been demonstrated in mice, as there is no platelet aggregation, no
hemolysis, and no disturbance in the hematological formula. The safety of the azabisphosphonate-
dendrimer has been assessed also with non-human primates (cynomolgus monkeys) which received repeated
injections, as a de-risking pre-clinical test. Biochemical, hematological, and all immunological parameters in peripheral blood remained within a normal physiological range throughout the study, and all survived well. Other phosphorous
dendrimers also display anti-inflammatory properties in vivo, in particular
dendrimers functionalized with
mannose derivatives, which prevent acute
lung diseases when given orally (per os) to mice. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Emerging Technologies Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease.