Synthesis of cationic branched tea polysaccharide derivatives for targeted delivery of siRNA to hepatocytes

The cationic branched tea polysaccharide (CTPSA) derivative bearing N-acylurea and 3-(dimethylamino)-1-propylamine residues was synthesized and characterized using FTIR and 1H NMR spectroscopy. A nonspecific siRNA (NsiRNA) was used as a model molecule of functional siRNA that could downregulate over-expressed glycometabolism enzymes in the liver. The result from the agarose gel electrophoresis confirmed that the CTPSA and NsiRNA could form stable complexes when their weight ratio was larger than 18. The zeta potentials and sizes of the complexes were in the range of +8–+15 mv and 120–150 nm, respectively. The CTPSA/NsiRNA complex was observed as nanoparticles with a spherical shape of approximately 100 nm using scanning electron microscopy. The CTPSA derivative and the CTPSA/NsiRNA complexes exhibited lower cytotoxicity in HL-7702 cells when compared with the branched PEI (bPEI) and bPEI/NsiRNA complexes assessed by the Cell Counting Kit-8 assay. The results of flow cytometric analysis and laser confocal microscopy indicated that the CTPSA derivative could effectively target the transfer of the NsiRNA to HL-7702 cells. This work provides a potential approach to promote the CTPSA derivative as a nonviral vector for targeted delivery of functional siRNA to hepatocytes.