Cylindrical Brush Polymers with Polysarcosine Side Chains: A Novel Biocompatible Carrier for Biomedical Applications

Cylindrical brush polymers constitute promising polymeric drug delivery systems (nanoDDS). Because of the densely grafted side chains such structures may intrinsically exhibit little protein adsorption (“stealth” effect) while providing a large number of functional groups accessible for bioconjugation reactions. Polysarcosine (PSar) is a highly water-soluble, nonionic and nonimmunogenic polypeptoid based on the endogenous amino acid sarcosine (<i>N</i>-methyl glycine). Here we report on the synthesis, characterization and biocompatibility of cylindrical brush polymers with either polysarcosine side chains or poly-l-lysine-<i>b</i>-polysarcosine side chains. The latter leads to block copolypept­(o)­id based core–shell cylindrical brushes with a cationic poly-l-lysine (PLL) core and a neutral polysarcosine corona. The cylindrical brush polymers were prepared by ring-opening polymerization of the respective N-carboxyanhydrides (NCA) from a macroinitiator chain. Preliminary experiments on complex formation with siRNA demonstrate that a core–shell cylindrical brush polymer may complex on average up to 270 RNA molecules amounting to a high loading efficiency of N⁺/P^– = 1.1. No bridging between cylindrical brushes leading to larger aggregates is observed. In vitro studies on the silencing of the expression of ApoB100, which is abundantly expressed in AML-12 hepatocytes, induced by siRNA-cylindrical core–shell brush complexes showed high efficiency, leading to a knock-down efficiency of ApoB100 mRNA of 70%