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Theranostics 2014; 4(5):487-497. doi:10.7150/thno.8263 This issue Cite
Research Paper
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,
3. Department of Gastroenterology, The Tenth People's Hospital of Shanghai, Tongji University, Shanghai, 20072, China
4. CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, National Center for Nanoscience & Technology of China, Beijing 100190, China.
5. Department of Cell and Developmental Biology, Weill Cornell Medical College, New York, NY10065, United States
* These authors contributed equally.
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.
Keywords: mesoporous silica nanoparticle, siRNA, delivery, cancer therapy, gene silencing