Self-assembly of four generations of RNA dendrimers for drug shielding with controllable layer-by-layer release.
Self-assembly of four generations of RNA dendrimers for drug shielding with controllable layer-by-layer release.
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DOI：
10.1039/d0nr02614j
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发表时间：
2020-07
期刊：
影响因子：
6.7
通讯作者：
Xin Li;Mario Vieweger;Peixuan Guo
中科院分区：
文献类型：
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作者：
Xin Li;Mario Vieweger;Peixuan Guo
化学树枝状大分子具有单分散性、多价性和支化结构等优点，是一种很有前途的药物载体。利用自组装及其固有的负电荷，我们使用RNA作为构建树枝状聚合物的积木，以消除复杂的合成程序和阳离子电荷相关的毒性。通过固相化学合成产生的寡核糖核苷酸允许大规模制造同源RNA树状聚合物。利用RNA纳米技术的概念，能够可控地生产具有逐层释放能力的从G1、G2、G3到G4代的树枝状聚合物。已经报道了将官能团缀合到单独的RNA链中以及将官能化的RNA链在不同位点并入树枝状聚合物中。负载到RNA树枝状聚合物中的抗癌药物显示出与游离药物相当的癌细胞抑制效果。细胞结合配体和疏水性药物在树枝状聚合物内的包封分别显著降低了细胞结合和蛋白质结合的效率，证明了RNA树枝状聚合物的屏蔽效应。研究结果表明，RNA树枝状聚合物在疏水性药物的体内递送、屏蔽和控制释放方面具有潜在的应用前景。
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 G1, G2, G3, to G4 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.