Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, 1365 Clifton Rd, Atlanta, GA, 30322, USA.
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, 1760 Haygood Dr, Atlanta, GA, 30322, USA.
Angew Chem Int Ed Engl. 2017 Dec 11;56(50):16023-16027. doi: 10.1002/anie.201709485. Epub 2017 Nov 15.
Short interfering RNA (siRNA) is a promising molecular tool for cancer therapy, but its clinical success is limited by the lack of robust in vivo delivery systems. Rationally designed DNA nanoparticles (DNPs) have emerged as facile delivery vehicles because their physicochemical properties can be precisely controlled. Nonetheless, few studies have used DNPs to deliver siRNAs in vivo, and none has demonstrated therapeutic efficacy. Herein, we constructed a number of DNPs of rectangular and tubular shapes with varied dimensions using the modular DNA brick method for the systemic delivery of siRNA that targets anti-apoptotic protein Bcl2. The siRNA delivered by the DNPs inhibited cell growth both in vitro and in vivo, which suppressed tumor growth in a xenograft model that specifically correlated with Bcl2 depletion. This study suggests that DNPs are effective tools for the systemic delivery of therapeutic siRNA and have great potential for further clinical translation.
短干扰 RNA（siRNA）是一种很有前途的癌症治疗分子工具，但由于缺乏强大的体内递送系统，其临床应用受到限制。经过合理设计的 DNA 纳米颗粒（DNP）作为一种易于操作的递送载体应运而生，因为其理化性质可以被精确控制。然而，很少有研究使用 DNP 在体内递送 siRNA，也没有研究证明其治疗效果。在此，我们使用模块化 DNA 积木方法构建了一系列具有不同尺寸的矩形和管状 DNA 纳米颗粒，用于递送针对抗凋亡蛋白 Bcl2 的 siRNA 的系统递送。由 DNP 递送的 siRNA 不仅在体外而且在体内都抑制了细胞生长，这抑制了在异种移植模型中的肿瘤生长，该模型与 Bcl2 的耗竭特异性相关。本研究表明，DNP 是一种有效的治疗性 siRNA 系统递送工具，具有很大的临床转化潜力。
