1. MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou, 510275, China, ; 2. Department of Nanomedicine, Houston Methodist Research Institute, Houston, Texas 77030, United States.
2. Department of Nanomedicine, Houston Methodist Research Institute, Houston, Texas 77030, United States.
Theranostics. 2014 Feb 15;4(5):487-97. doi: 10.7150/thno.8263. eCollection 2014.
Effective delivery holds the key to successful in vivo application of therapeutic small interfering RNA (siRNA). In this work, we have developed a universal siRNA carrier consisting of a mesoporous silica nanoparticle (MSNP) functionalized with cyclodextrin-grafted polyethylenimine (CP). CP provides positive charge for loading of siRNA through electrostatic interaction and enables effective endosomal escape of siRNA. Using intravital microscopy we were able to monitor tumor enrichment of CP-MSNP/siRNA particles in live mice bearing orthotopic MDA-MB-231 xenograft tumors. CP-MSNP delivery of siRNA targeting the M2 isoform of the glycolytic enzyme pyruvate kinase (PKM2) resulted in effective knockdown of gene expression in vitro and in vivo. Suppression of PKM2 led to inhibition of tumor cell growth, invasion, and migration.
有效的递送是治疗性小干扰 RNA（siRNA）体内应用成功的关键。在这项工作中，我们开发了一种由环糊精接枝聚亚乙基亚胺（CP）功能化的介孔硅纳米颗粒（MSNP）组成的通用 siRNA 载体。CP 通过静电相互作用为 siRNA 的负载提供正电荷，并使 siRNA 有效逃离内涵体。通过活体显微镜，我们能够监测携带原位 MDA-MB-231 异种移植肿瘤的活小鼠中 CP-MSNP/siRNA 颗粒的肿瘤富集。CP-MSNP 递送靶向糖酵解酶丙酮酸激酶（PKM2）M2 同工型的 siRNA，导致体外和体内基因表达的有效敲低。PKM2 的抑制导致肿瘤细胞生长、侵袭和迁移的抑制。
