Directed Interactions of Block Copolypept(o)ides with Mannose-binding Receptors: PeptoMicelles Targeted to Cells of the Innate Immune System

Core‐shell structures based on polypept(o)ides combine stealth‐like properties of the corona material polysarcosine with adjustable functionalities of the polypeptidic core. Mannose‐bearing block copolypept(o)ides (PSar‐block‐PGlu(OBn)) have been synthesized using 11‐amino‐3,6,9‐trioxa‐undecyl‐2,3,4,6‐tetra‐O‐acetyl‐O‐α‐D‐mannopyranoside as initiator in the sequential ring‐opening polymerization of α‐amino acid N‐carboxyanhydrides. These amphiphilic block copolypept(o)ides self‐assemble into multivalent PeptoMicelles and bind to mannose‐binding receptors as expressed by dendritic cells. Mannosylated micelles showed enhanced cell uptake in DC 2.4 cells and in bone marrow‐derived dendritic cells (BMDCs) and therefore appear to be a suitable platform for immune modulation. Polypeptoide‐block‐polypeptide copolymers (polypept(o)ides) have raised first attention as a versatile material for the next generation of nano‐drug delivery systems. By the use of functional initiators, mannose‐bearing block copolypept(o)ides (PSar‐block‐PGlu(OBn)) can be obtained, which self‐assemble into multivalent PeptoMicelles. These mannosylated micelles can interact with mannose receptors as expressed by dendritic cells.