Tetraethylenepentamine-Coated β Cyclodextrin Nanoparticles for Dual DNA and siRNA Delivery

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Tetraethylenepentamine-coated β-cyclodextrin (TEPA-BCD) nanoparticles were synthesized, characterized, and evaluated for targeted cell delivery of plasmid DNA and siRNA. The cationic TEPA coating provided ideal zeta potential and effective nucleic acid binding ability. When transfecting plasmid encoding green fluorescent protein (GFP) by TEPA-BCD, excellent GFP expression could be achieved in multiple cell lines. In addition, siRNA transfected by TEPA-BCD suppressed target GFP gene expression. We showed that TEPA-BCD internalization was mediated by energy-dependent endocytosis via both clathrin-dependent and caveolin-dependent endocytic pathways. TEPA-BCD nanoparticles provide an effective means of nucleic acid delivery and can act as potential carriers in future pharmaceutical application.

Syntheis route: The 6-hydroxyl groups of BCD were activated with tosyl chloride. After nucleophilic displacement by ethylenediamine (EDA), TEPA-BCD nanoparticles were synthesized by the crosslinking reaction of EDA-BCD and TEPA via glutaraldehyde (GA). The synthesis of TEPA-BCD nanoparticles is demonstrated in the featured scheme.

TEPA-modified BCD demonstrated a nanometer size, positive surface charge, minimal cytotoxicity, great electrostatic interaction with nucleic acid, and efficient delivery. In both ARPE cells and 3T3 cells, TEPA-BCD entered cells through clathrin- and caveolae-mediated endocytosis. TEPA-BCD/plasmid DNA mediated high gene expression and TEPA-BCD/siRNA displayed efficient gene silencing. The TEPA-BCD provides a promising platform for delivery of therapeutic nucleic acids in vitro and warrants further development of its potential for in vivo delivery.

Chi-Hsien Liu ,Pei-Yin Shih, Cheng-Han Lin, Yi-Jun Chen, Wei-Chi Wu, Chun-Chao Wang (2022) Tetraethylenepentamine-Coated β Cyclodextrin Nanoparticles for Dual DNA and siRNA Delivery. Pharmaceutics , 14(5), 921; https://doi.org/10.3390/pharmaceutics14050921

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