Novel Biodegradable Gene Vectors Based On Polysaccharide-Grafted-Poly(Aspartic Acid)S

Gene therapy has presented remarkable potential in the clinical therapy for congenital genetic defects and acquired diseases. The development of gene vectors with low cytotoxicity and high transfection efficiency is important for successful gene therapy. Generally, gene vectors are divided into two types, including viral and non-viral gene vectors. Compared with viral gene vectors, non-viral ones as the priority of gene therapy possess advantages such as noninfectivity, unlimited carrier capacity, controllability for chemical structure, large-scale manufacturability, low toxicity and low immunogenicity. However, there were not ideal non-viral vectors with high efficiency for gene delivery in the present. It is still a challenge to develop gene vectors with safety and high efficiency.Natural polysaccharides possess amounts of characteristics containing renewability and good biocompatibility. The design of safe and highly efficient cationic polymer gene carriers based on polysaccharide is an effective method. Poly (aspartic acid)s has caused widespread attention in the field of gene vectors due to their excellent properties such as low cytotoxicity, outstanding biocompatibility and biodegradability. In this article, a series of cationic gene carriers based on polysaccharide-grafted-poly (aspartic acid)s with low cytotoxicity, high efficiency and biodegradability were proposed. The main work was shown as follows:1. A series of polysaccharide-grafted-PBLAs with different molecular weights were synthesized through the ring-opening polymerization of monomer BLA-NCA initiated by amino groups of polysaccharide modified by ethanediamine (ED). Then, polysaccharide-grafted-PBLAs were aminolyzed by excess ED to produce the corresponding polysaccharide-grafted-PAsp-EDs. Degradation, cell viability and in vitro transfection assays were conducted to certify the biological properties of cationic polymers synthesized in this work. And the results demonstrated that CS-PAsp-EDs possessed the best properties as gene vectors.2. Poly(aspartic acid)s-grafted chitosan-cyclodextrin conjugates (CCPs) were prepared via ring-opening polymerization of BLA with initiators ED-modified-chitosan-cyclodextrin conjugates. Folic acid (FA) ligand targeting gene vectors CCPE-FAs was produced via the host-guest interaction between the cyclodextrin of CCPE and Ad-modified FA (Ad-FA). The ternary polyplexes prepared by layer-by-layer assembly with the suitable amount of ligand produce excellent gene transfection abilities in the FR-positive tumor cells in Hela and C6.