Scavenger Receptor A-Mediated Targeting of Carboxylated Polyrotaxanes to Macrophages and the Impacts of Supramolecular Structure.

Because macrophages are involved in the pathology of many diseases, targeting delivery of therapeutic molecules to macrophages is important issue. Polyrotaxanes (PRXs) composed of multiple cyclodextrins threaded with a linear polymer were utilized as a therapeutic agent for metabolic disease and for regulating cellular metabolism. For targeting delivery of PRXs to macrophages, carboxyethyl ether group-modified PRXs (CEE-PRXs) are designed for promoting interaction to macrophage scavenger receptor class A (SR-A). The cellular internalization of anionic CEE-PRXs in SR-A-positive macrophage-like cells (RAW264.7) is remarkably higher than that of nonionic PRX, whereas the cellular internalization efficiency in SR-A-negative cells is comparable between anionic and nonionic PRX. Furthermore, the molecular weight of axle polymer and the number of CEE groups modified on PRX are found to be the predominant factors governing cellular internalization efficiency in SR-A-positive RAW264.7 cells. Thus, CEE-PRXs are a promising design for targeting delivery of PRXs to macrophages.