Assembling defined DNA nanostructures with anticancer drugs: a metformin/DNA complex nanoplatform with a synergistic antitumor effect for KRAS-mutated lung cancer therapy

作者全名："Qian, Hang; Wang, Dong; He, Binfeng; Liu, Qian; Xu, Yu; Wu, Di; Chen, Chunfa; Zhang, Wen; Leong, David Tai; Wang, Guansong"

作者地址："[Qian, Hang; Wang, Dong; He, Binfeng; Liu, Qian; Xu, Yu; Wu, Di; Chen, Chunfa; Zhang, Wen; Wang, Guansong] Third Mil Med Univ, Xinqiao Hosp, Inst Resp Dis, Chongqing 400037, Peoples R China; [Wang, Dong] Nanjing Univ, Jinling Hosp, Dept Resp Med, Nanjing, Peoples R China; [He, Binfeng] Fudan Univ, Zhongshan Hosp, Dept Pulm & Crit Care Med, Shanghai, Peoples R China; [Liu, Qian] Chongqing Med Univ, Lab Teaching & Management Ctr, Lab Pharm & Chem, Chongqing, Peoples R China; [Liu, Qian] Chongqing Med Univ, Lab Teaching & Management Ctr, Lab Tissue & Cell Biol, Chongqing, Peoples R China; [Leong, David Tai] Natl Univ Singapore, Dept Chem & Biomol Engn, Singapore, Singapore"

通信作者："Wang, GS (通讯作者)，Third Mil Med Univ, Xinqiao Hosp, Inst Resp Dis, Chongqing 400037, Peoples R China.; Leong, DT (通讯作者)，Natl Univ Singapore, Dept Chem & Biomol Engn, Singapore, Singapore."

来源：NPG ASIA MATERIALS

ESI学科分类：MATERIALS SCIENCE

WOS号：WOS:000864638100001

JCR分区：Q1

影响因子：9.7

年份：2022

卷号：14

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要："Herein, a strategy is proposed to simultaneously deliver the small-molecule drug metformin and siRNA with self-assembled DNA nanostructures. The biomedical application of DNA nanostructures is highly promising but still in its infancy. DNA nanostructures as drug delivery vehicles are conventionally synthesized in a magnesium-containing buffer. We propose using an anticancer drug to assemble DNA nanostructures and deliver them with siRNA for synergistic anticancer therapy. The metformin cargo induces DNA self-assembly into well-defined, uniform nanostructures, producing a drug-DNA nanocomplex with multiple functionalities for cancer therapy. Both tile-based and DNA origami structures can be assembled with metformin. The as-prepared metformin/DNA nanocomplex showed high structural and thermal stability and enzymatic resistance in physiological settings. The metformin in the nanocomplex and the KRAS(G12C) siRNA exerted a strong, synergistic antitumor effect against KRAS-mutated non-small cell lung cancer (NSCLC) both in vitro and in vivo by suppressing the RAS/AKT/mTOR and AMPK/AKT/mTOR signaling pathways. The current study suggests that the assembly of complex DNA nanomaterials with carefully chosen small molecules is key to endowing DNA nanostructures with new functionalities and subsequently expanding their applications in multidisciplinary research fields."

基金机构："National Natural Science Foundation of China [32071379, 81670047, 82070071]; National Natural Science Foundation of Chongqing, China [cstc2021ycjh-bgzxm0011]"

基金资助正文："We thank Prof. Pengfei Wang from Shanghai Jiao Tong University for his support with DNA origami design and Prof. Qiaonan Guo and Dr. Yangfan Lv from the Pathology Department of Xinqiao Hospital for their technical support with IHC experiments. We thank the College of Pharmaceutical Sciences, Southwest University for technical assistance in AFM imaging (Bruker Multimode 8). This work was supported by the National Natural Science Foundation of China (32071379, 81670047, 82070071) and the National Natural Science Foundation of Chongqing, China (cstc2021ycjh-bgzxm0011)."