Solution Properties and Potential Biological Applications of Zwitterionic Poly(ε‑<i>N</i>‑methacryloyl‑l‑lysine)

Poly­(ε-<i>N</i>-methacryloyl-l-lysine) (PMALys) was synthesized by free radical polymerization yielding a zwitterionic polymer with <i>M</i>_w = 721 000 g mol^–1. The polymer dissolves in pure water as well as in aqueous salt solution up to 5 M NaClO₄ and over wide range of pH values (1.3 ≤ pH ≤ 12.7) as single chains without any sign for aggregate formation. The zwitterionic polymer shows an expanded random coil structure at and close to isoelectric conditions and further expands upon addition of acid and base, respectively. The polymer fulfills four major prerequisites for a promising nano carrier in potential biomedical applications: (1) It is biocompatible, indicated by a low cytotoxicity. (2) It does not aggregate in concentrated human blood serum solution. (3) The amino groups in the polyzwitterion may be utilized for conjugations as demonstrated by labeling reactions with AlexaFluor488. (4) Cell uptake experiments revealed little uptake in bone marrow dendritic cells, i.e., little <i>unspecific</i> uptake, which is mandatory for a successful specific targeting of cells. Finally, upon addition of Zn²⁺ ions the polyzwitterions may be converted into polycations which are demonstrated to form complexes with DNA. Such complexes may be advantageous for application in gene transfection studies