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 (N-methyl
glycine). Here we report on the synthesis, characterization and biocompatibility
of cylindrical brush polymers with either polysarcosine side chains
or poly-l-lysine-b-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%.