School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, P.R. China.
Biomater Sci. 2018 Jul 24;6(8):2122-2129. doi: 10.1039/c8bm00491a.
The development of delivery systems for small interfering RNA (siRNA) plays a key role in its clinical application. As the major delivery systems for siRNA, cationic polymer- or lipid-based vehicles are plagued by inherent issues. As proof of concept, a disulfide bond-containing amphiphilic Janus dendrimer (ssJD), which could be conveniently synthesized and readily scaled up with high reproducibility, was explored as a siRNA delivery system to circumvent these issues. The cationic hydrophilic head of this Janus dendrimer ensured strong and stable binding with negatively charged siRNA via electrostatic interactions, and the loaded siRNA was rapidly released from the obtained complexes under a redox environment. Therefore, after efficient internalization into tumor cells, redox-sensitive dendrimersome (RSDs)/siRNA exhibited significantly improved gene silencing efficacy.
在小干扰 RNA（siRNA）的临床应用中，其递释系统的发展起着关键作用。作为 siRNA 的主要递释系统，阳离子聚合物或脂质载体存在固有问题。作为概念验证，一种含二硫键的两亲性 Janus 树状大分子（ssJD）被探索为 siRNA 递释系统以规避这些问题，它可以方便地合成，并具有高重现性的放大规模。这种 Janus 树状大分子的阳离子亲水头确保了通过静电相互作用与带负电荷的 siRNA 进行强而稳定的结合，并且负载的 siRNA 可以在氧化还原环境下从获得的复合物中迅速释放。因此，在有效内化进入肿瘤细胞后，氧化还原敏感的树状聚合物囊泡（RSD）/siRNA 表现出显著提高的基因沉默效果。
