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Chemical dendrimers have been shown to be a promising drug delivery platform due to their advantageous properties such as monodispersity, multivalency and branched structure. Taking advantage of self-assembly and its intrinsic negative charge, we used RNA as the building block for dendrimer construction to eliminate complex synthesis procedures and cationic charge-related toxicity. 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 dendrimers with generations from G 1 , G 2 , G 3 , to G 4 with layer-by-layer release capability. The conjugation of functional groups into individual RNA strands and the incorporation of functionalized RNA strands into the dendrimers at different sites have been reported. Anticancer drugs loaded into RNA dendrimers showed comparable cancer cell inhibition effect to free drugs. 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.

Self-assembly of four generations of RNA dendrimers for drug shielding with controllable layer-by-layer release