CD44, a well-documented cell surface receptor, is involved in cell proliferation, migration, signaling, adhesion, differentiation and angiogenesis, which are important properties for normal and cancerous cell function. We recently developed particle clusters coated with hyaluronan, CD44 ligand, (termed gagomers; GAGs), and showed that they can deliver paclitaxel, and separately Mitomycin C (MMC) directly into CD44-overexpressing tumors in mouse tumor models. We also showed that GAGs can bind to primary head and neck cancers (HNC) and deliver MMC to these cells in an efficacious manner, but not to normal cells taken from the same patient. Here we show that GAGs can entrap high amounts of RNAi payloads and deliver them directly into tumor-bearing mice in a selective manner without any bystander delivery. Next, we show that RNAi formulated in GAGs do not elevate cytokines, or induce interferon response or activate complement in human peripheral blood mononuclear cells, mice and rats. In addition, histology sections do not reveal any pathological changes in organs of the mononuclear phagocytic system (MPS) such as the liver, spleen, and lungs. In addition, no liver enzyme release or changes in metabolic parameters are observed. These results demonstrate the selective recognition of GAGs towards cancerous cells with an exquisite capability to deliver RNAi payloads and induce robust therapeutic gene silencing together with excellent safety profile. These credentials position GAGs as an attractive alternative to cationic formulations, which might be applicable in many types of cancer.<br/><br/><br/>

Gagomers: Safe, lipid-based- nanoparticle clusters coated with a glycosaminoglycan for systemic delivery of therapeutic payloads

249th National Meeting (2015)

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