0000000000384478
AUTHOR
David Schäffel
SiRNA-mediated in vivo gene knockdown by acid-degradable cationic nanohydrogel particles
Cationic nanohydrogel particles have become an attractive tool for systemic siRNA delivery, but improvement of their in vivo tolerance is desirable, especially to prevent potential long term side effects by tissue and cellular accumulation. Here, we designed novel ketal cross-linked cationic nanohydrogel particles that were assessed for reduced tissue accumulation and robust siRNA delivery in vitro and in vivo. An oligo-amine cross-linker equipped with a ketal moiety in its core was synthesized and applied to nanohydrogel cross-linking of self-assembled reactive ester block copolymers in DMSO. The resulting acid-sensitive cationic nanoparticles spontaneously disassembled over time in acidic…
Solution Properties and Potential Biological Applications of Zwitterionic Poly(ε-N-methacryloyl-l-lysine)
Poly(e-N-methacryloyl-l-lysine) (PMALys) was synthesized by free radical polymerization yielding a zwitterionic polymer with Mw = 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 …
Selective Uptake of Cylindrical Poly(2-Oxazoline) Brush-AntiDEC205 Antibody-OVA Antigen Conjugates into DEC-Positive Dendritic Cells and Subsequent T-Cell Activation
To achieve specific cell targeting by various receptors for oligosaccharides or antibodies, a carrier must not be taken up by any of the very many different cells and needs functional groups prone to clean conjugation chemistry to derive well-defined structures with a high biological specificity. A polymeric nanocarrier is presented that consists of a cylindrical brush polymer with poly-2-oxazoline side chains carrying an azide functional group on each of the many side chain ends. After click conjugation of dye and an anti-DEC205 antibody to the periphery of the cylindrical brush polymer, antibody-mediated specific binding and uptake into DEC205(+) -positive mouse bone marrow-derived dendri…