Highly effective inhibition of lung cancer growth and metastasis by systemic delivery of siRNA via multimodal mesoporous silica-based nanocarrier

Biomaterials. 2014 Dec;35(38):10058-69. doi: 10.1016/j.biomaterials.2014.09.003. Epub 2014 Sep 29.

Abstract

Lung cancer has been the leading type of cancers with regard to mortality and mobility. New versions of RNAi-based therapy are greatly required to tackle the challenges of lung cancer. 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 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.

Keywords: Lung cancer therapy; Mesoporous silica nanoparticles; Metastasis; Systemic delivery; VEGF; siRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Diffusion
  • Genetic Therapy / methods*
  • Humans
  • Mice
  • Mice, Nude
  • Nanocapsules / chemistry*
  • Nanocapsules / ultrastructure
  • Nanopores / ultrastructure
  • Neoplasms, Experimental / genetics
  • Neoplasms, Experimental / secondary*
  • Neoplasms, Experimental / therapy*
  • Porosity
  • RNA, Small Interfering / administration & dosage*
  • RNA, Small Interfering / genetics*
  • Transfection / methods
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / therapeutic use*

Substances

  • Nanocapsules
  • RNA, Small Interfering
  • Vascular Endothelial Growth Factor A