Due to their nanometric size, dendrimers have been considered as potentially suitable as new vehicles for drug delivery since their infancy. The association of a dendrimer and a drug may occur in different ways, either through covalent or non-covalent interactions. A non-covalent interaction can be the simple encapsulation inside dendrimers that enhances the solubility of lipophilic drugs in water, or electrostatic interactions between the surface and charged drugs (or DNA, RNA, or siRNA). The covalent association may occur through stable bonds, in particular for dendrimers that are considered as active per se, or through cleavable bonds that should be cleaved only when reaching the target (often cancerous cells). In addition, the full structure of the dendrimer can be disassembled under the influence of a trigger such as pH variations. This review will present these strategies and their consequences for drug delivery.

Dendrimers are highly branched “tree-like” polymers that have demonstrated therapeutic potential in drug delivery, medical imaging, and tissue engineering in recent years. In addition, we have shown that an azabisphosphonate (ABP)–capped dendrimer selectively targets monocytes and directs them toward anti-inflammatory activation. We explored this property to assess the therapeutic potential of dendrimer ABP in the treatment of an inflammatory disease, rheumatoid arthritis. Intravenous injections of dendrimer ABP inhibited the development of inflammatory arthritis in two animal models: IL-1ra^−/− mice and mice undergoing K/BxN serum transfer. Suppression of disease was characterized by normal synovial membranes, reduced levels of inflammatory cytokines, and the absence of cartilage destruction and bone erosion. Dendrimer ABP also exhibited anti-osteoclastic activity on mouse and human cells, mediated by c-FMS (cellular-feline McDonough strain sarcoma virus oncogene homolog) inhibition. These preclinical demonstrations suggest the potential use of dendrimer ABP as a nanotherapeutic for rheumatoid arthritis.

Overview of the use of dendrimers in combination with encapsulated and conjugated natural products and analogues as anti-cancer agents.

Guest editors Anne-Marie Caminade, Deyue Yan and David K. Smith introduce the Dendrimers and Hyperbranched Polymers issue of Chemical Society Reviews