3 years ago

Systemic Delivery of siRNA by DNA Nanoparticles Targeting Bcl2 in Cancer Cell Growth

Zhengjia Chen, Sreenivas Nannapaneni, Dongsheng Wang, Christopher C. Griffith, Zhixiang Zhao, Pengfei Wang, Yonggang Ke, Chao Zhang, Zhuo G. Chen, Mohammad Aminur Rahman, Dong Moon Shin, Selwyn J. Hurwitz
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 since 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 targeting an antiapoptotic protein Bcl2. siRNA delivered by 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 systemic delivery of therapeutic siRNA and have great potential for further clinical translation.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/anie.201709485

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