4.7 Article

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

Journal

COLLOIDS AND SURFACES B-BIOINTERFACES
Volume 198, Issue -, Pages -

Publisher

ELSEVIER
DOI: 10.1016/j.colsurfb.2020.111491

Keywords

Curdlan; Folate tumor targeting; Bcl-2 siRNA delivery

Funding

  1. National Natural Science Foundation of China [21664011]

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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.
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.

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