Construction and characterization of folate-functionalized curdlan-trilysine siRNA delivery platform for in vivo hepatic carcinoma treatment

RNA interference technology is a powerful tool with substantially clinical prospects for carcinoma therapy, in which efficiency and specificity of delivery of dsRNA remains a critical issue. Herein, aiming at delivery of dsRNA in efficient and safe way, we constructed targeting delivery platform (CTL-PEG-FA) by grafting curdlan with trilysine through click reaction, then modifying with PEG linked folic acid. The CTL-PEG-FA vector exhibited excellent gene binding capacity to condense siRNA and dramatically reduced cytotoxicity. Increased cell uptake of CTL-PEG-FA/Bcl-2 siRNA was achieved by the synergism of folate mediated endocytosis and charge interaction, and further causing severe HepG2 cells injury through apoptosis mechanism after down-regulation of Bcl-2 protein. In vivo experiments, CTL-PEG-FA/Bcl-2 siRNA complex distinctly accumulated in tumor site and significantly inhibited the growth of tumor, while no obvious toxicity was observed. Therefore, well-performed CTL-PEG-FA with excellent biocompatibility, has the potential to be the candidate of gene therapy for clinical applications.

Automated summary

RNA interference technology shows great potential in carcinoma therapy, but the efficiency and specificity of dsRNA delivery are crucial. A targeting delivery platform (CTL-PEG-FA) was constructed to efficiently and safely deliver dsRNA, which exhibited excellent gene binding capacity and reduced cytotoxicity. In vivo experiments showed that CTL-PEG-FA/Bcl-2 siRNA complex effectively accumulated at the tumor site, leading to tumor growth inhibition without obvious toxicity, suggesting its potential for clinical gene therapy applications.