A spermine conjugated stearic acid-g-chitosan oligosaccharide polymer with different types of amino groups for efficient p53 gene therapy

• The SP-CSOSA polymer combined amounts of primary and secondary amine groups.
• It effectively condensed pDNA and promoted gene escape from endo-lysosomes.
• SP-CSOSA proved an effective vector for wild-type p53 gene.
• SP-CSOSA/p53 complexes resulted in obvious cell apoptosis and G1 arrest.

The effect of various amino groups on gene vector is different. In order to combine their effect in one vector and finally promote the transfection efficiency, a biogenic tetra-amine spermine was introduced to modify the stearic acid-grafted chitosan oligosaccharide (CSOSA) polymer to build a new gene delivery system. The spermine linked CSOSA (SP-CSOSA) polymer consists two types of amino groups with 73.3%, 19.3% of all nitrogen atoms for primary and secondary amine groups, respectively. The SP modified CSOSA showed strong DNA condensation capability and obviously enhanced proton binding ability especially at about pH 5.0, which significantly promoted the escape of SP-CSOSA/pDNA complexes from endo-lysosoms. Moreover, the transfection efficiency at the N/P ratio of 10 could compete with that of Lipofectamine 2000 and PEI 25K, but with lower cytotoxicities. The therapeutic wild type p53 gene transfected by the SP-CSOSA polymer restored the function of aberrant p53 gene and induced obvious cell apoptosis and G1 phase arrest. We concluded that the new vector SP-CSOSA polymer proved to be a potential delivery system for gene therapy.

Formation and function process of the gene complexes based on stearic acid (SA) and spermine (SP) modified chitosan oligosaccharide (SP-CSOSA) polymer.Figure optionsDownload as PowerPoint slide