Poster abstracts

Poster number 59 submitted by Xin Li

Deploy RNA G1-G4 dendrimers self-assembled from motifs for drug sheltering with controllable layer-by-layer release

Xin Li (Center for RNA Nanobiotechnology and Nanomedicine, College of Pharmacy, Dorothy M. Davis Heart and Lung Research Institute, James Comprehensive Cancer Center, The Ohio State University), Peixuan Guo (Center for RNA Nanobiotechnology and Nanomedicine, College of Pharmacy, Dorothy M. Davis Heart and Lung Research Institute, James Comprehensive Cancer Center, The Ohio State University)

Abstract:
Dendrimers are polymeric molecules with defined and monodisperse branched structures, which have been used as drug delivery platforms due to their unique properties. Taking advantage of the self-assembly and programmability property of RNA, we used three-way junction RNA nanoparticles as the building block for dendrimer construction to achieve simple synthesis procedure and favorable biodistribution profile. Oligo ribonucleotides produced by solid phase chemical synthesis allow the large-scale manufacture of homologous RNA dendrimers. Employing concepts from RNA nanotechnology enabled the controllable production of four generations of RNA dendrimers from G1, G2, G3, to G4 with temperature-triggered layer-by-layer release capability. The conjugation of various functional groups into individual RNA strands and the incorporation of functionalized RNA strands into the dendrimers at different sites have been reported. RNA dendrimers conjugated with multiple copies of anticancer drug, paclitaxel, showed comparable cancer cell inhibition effect to free drugs. Furthermore, the encapsulation of cell binding ligands and hydrophobic drugs within the dendrimer significantly reduced the efficiency of cell binding and protein binding respectively, demonstrating the shielding effect of RNA dendrimers. The results imply a potential application of RNA dendrimer for delivery, shielding and controlled release of hydrophobic drugs in vivo.

References:
1. X. Li, M. Vieweger and P. Guo, Nanoscale, 2020, 16514–16525.
2. S. Guo, M. Vieweger, K. Zhang, H. Yin, H. Wang, X. Li, S. Li, S. Hu, A. Sparreboom, B. M. Evers, Y. Dong, W. Chiu and P. Guo, Nat. Commun., 2020, 11, 972.
3. A. Sharma, F. Haque, F. Pi, L. S. Shlyakhtenko, B. M. Evers and P. Guo, Nanomedicine Nanotechnology, Biol. Med., 2016, 12, 835–844.

Keywords: RNA nanotechnology, RNA dendrimer, Drug delivery and shielding