Structurally Flexible Triethanolamine Core PAMAM Dendrimers Are Effective Nanovectors for DNA Transfection in Vitro and in Vivo to the Mouse Thymus

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Liu, Xiaoxuan | Wu, Jiangyu | Yammine, Miriam | Zhou, Jiehua | Posocco, Paola | Viel, Stéphane | Liu, Cheng | Ziarelli, Fabio | Fermeglia, Maurizio | Pricl, Sabrina | Victorero, Genevieve | Nguyen, Catherine | Erbacher, Patrick | Behr, Jean-Paul | Peng, Ling

Edité par HAL CCSD ; American Chemical Society

International audience. With the aim of developing dendrimer nanovectors with a precisely controlled architecture and flexible structure for DNA transfection, we designed PAMAM dendrimers bearing a triethanolamine (TEA) core, with branching units pointing away from the center to create void spaces, reduce steric congestion, and increase water accessibility for the benefit of DNA delivery. These dendrimers are shown to form stable nanoparticles with DNA, promote cell uptake mainly via macropinocytosis, and act as effective nanovectors for DNA transfection in vitro on epithelial and fibroblast cells and, most importantly, in vivo in the mouse thymus, an exceedingly challenging organ for immune gene therapy. Collectively, these results validate our rational design approach of structurally flexible dendrimers with a chemically defined structure as effective nanovectors for gene delivery, and demonstrate the potential of these dendrimers in intrathymus gene delivery for future applications in immune gene therapy.

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