SYNTHESIS OF BIOREDUCIBLE AND ACID LIABLE POLY(AMIDO AMINE)S VIA MICHAEL-ADDITION REACTIONS

摘要

@@The development of novel polymer-based carrier systems, which can protect and deliver gene to the cytoplasm, is a major key to gene therapy.1 Poly (amido amine)s (PAAs) are a family of water-soluble and biocompatible polymer which show great potential applications in gene delivery. Those polymers can be synthesized via Michael addition reaction of amines with bisacrylamide under mild condition.2 However, the slow degradation of amides in the backbone of PAA lowers the gene delivery efficiency, and results in long-term accumulation in the body and subsequent cellular toxicity. The Disulfide-contained cationic polymers are bioreducible, the disulfide bonds are stable in extracellular matrices while can be quickly cleaved inside the cells by reducing enzymes like glutathione reductase and sulfhydryl components like glutathione, since the concentration of these reducing species is about 100 times higher in the cytoplasm man mat in plasma.