High-order Assembly Towards Polysaccharide-Based Complex Coacervate Nanodroplets Capable of Targeting Cancer Cells.

High-order assembly plays a significant role in the formation of living organisms containing a large number of biomacromolecules, and thus enlightens the construction of nanomaterials that can load macromolecular payloads at a high efficiency. Herein, by choosing anionic hyaluronic acid (HA) as a model payload, we demonstrated how the electrostatic interaction induced high-order assembly can be utilized to load efficiently biomacromolecules into complex coacervate nanodroplets. The resultant assemblies were primarily composed of HA and cationic chitosan oligosaccharide/dextran (COS/Dex) nanogels, and had controllable structure while also exhibiting biological functionality. The HA in the assemblies is capable of targeting CD44-overexpressed tumor cells through CD44-mediated endocytic pathways which are elucidated herein. Therefore, this study provides a reliable approach for the efficient loading of macromolecular payloads into complex coacervate nanodroplets via electrostatic attraction induced high-order assembly.