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A cationic group has been quantitatively and selectively introduced into C6 position of each glucose units of Curdlan by “Click Chemistry” successfully. The resulting cationic Curdlan-Imidazole-lysine polymers (Cur-6-100Lys) exhibit excellent water solubility. Structure of the Cur-6-100Lys complexes was verified by FTIR and NMR spectroscopic measurements, and analysis of Cur-6-100Lys by GPC, DLS and SEM revealed that they have stoichiometric, nanosized spheroidal structures. Cytotoxicity measurement, electrophoretic mobility shift assay and EGFP-pDNA transfection have been carried out respectively. The results clearly show that Cur-6-100Lys nanocarriers have bound to dsDNA promptly, are less cytotoxic to both 7901 cells and HeLa cells, and are readily able to transport EGFP-pDNA into HepG2 cells. Our studies indicated that Cur-6-100Lys can potentially be used as a versatile nano platform for efficient gene delivery in living cells. [ABSTRACT FROM AUTHOR]

RNA interference (RNAi) is an evolutionarily conserved gene-silencing phenomenon that shows great promise for developing new therapies. However, the development of small interfering RNA (siRNA)-based therapies need to establish efficient delivery system that silences target genes with siRNA doses that is clinically feasible in humans. Here we report synthesis and in vivo study of a novel PEGylated curdlan-based nanoparticle, designated as 6AC-100PEG, obtained by conjugation of mPEG 2000 to 6-amino-6-deoxy-curdlan. The complex of siRNA/6AC-100PEG showed homogenous nanoparticles with an average diameter of 200 nm. MTT assay indicated that 6AC-100PEG does not have apparent cytotoxicity. Systemic administration of a complex of siapoB/6AC-100PEG significantly reduced the level of apoB mRNA in mouse liver, indicating that 6AC-100PEG can efficiently deliver siRNA to mouse liver and induce RNAi. Administration of siRNA/6AC-100PEG to mouse did not elevate liver enzyme level in the serum, indicating that 6AC-100PEG nanoparticle is a promising in vivo siRNA delivery agent. [ABSTRACT FROM AUTHOR]

• Triornithine grafted novel curdlan gene vector was fabricated by click chemistry. • Lactobionic acid ligands target deliver to liver cancer cells. • Curdlan-based carriers show lower cytotoxicity and higher binding capacity than PEI. • Final complex CTOL20% efficiently delivered siRNA into HepG2 cells. A long-anticipated cancer therapy would deliver the right type of therapeutic agents to the target in control with minimal systemic toxicity. The purpose of this study was to prepare lactosylated curdlan-triornithine nanocarriers (CTOLs), and target deliver gene to hepatoma cells. Structures and biophysical properties had been elucidated with physical and chemical methods. The results revealed that those functionalized polymers can completely condense the gene into spherical nanoparticles. Cytotoxicity assay, GFP-pDNA and siRNA transfection in vitro were implemented successively. Observations showed that CTOL 20% with the highest lactose acid substitution degree targeted delivered gene into HepG2 cells over expressing ASGPR receptors and had pretty gene knockdown efficiency over 70%. Meanwhile, the carriers showed excellent biocompatibility. Our studies demonstrated that CTOLs with lower toxicity and higher gene binding capacity may serve as a potential valuable platform that can be tailored to target the liver cancer cells for therapeutic gene. [ABSTRACT FROM AUTHOR]