Systemic Delivery Of Therapeutic Sirna By Multifunctional Mesoporous Silica-Based Nanocarrier Inhibits Lung Cancer Growth And Metastasis

RNAi-based therapy by targeting dysregulated genes has shown great promise in biomedical research but still newer versions of effective and safe delivery systems are required. In this study, we developed a novel siRNA delivery vector based on our magnetic mesoporous silica nanoparticles (M-MSNs) platform. This nanocarrier was constructed by loading siRNAs into the mesopores of M-MSNs, followed by polyethylenimine (PEI) capping, PEGylation and fusogenic peptide KALA modification. The resultant functionalized delivery system exhibited prolonged half-life in bloodstream, enhanced cell membrane translocation and endosomal escapablity, and favorable tissue biocompatibility and biosafety. Systemic application of vascular endothelial growth factor (VEGF) siRNA via this nanocarrier resulted in remarkable tumor suppression, both in subdermal and orthotopic lung cancer models, while tumor metastasis was also significantly reduced, overall leading to improved survival. In addition, the magnetic core of the particles and the functionalized fluorescence markers conveniently enabled in vivo imaging of target tissues. Taken together, this M-MSNs-based siRNA delivery vehicle has shown very favorable applicability for cancer therapy. Citation Format: Yijie Chen, Hongchen Gu, Weiliang Xia. Systemic delivery of therapeutic siRNA by multifunctional mesoporous silica-based nanocarrier inhibits lung cancer growth and metastasis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 718. doi:10.1158/1538-7445.AM2014-718