Assessment of drug delivery and anticancer potentials of nanoparticles-loaded siRNA targeting STAT3 in lung cancer, in vitro and in vivo

Jayeeta Das, Sreemanti Das, Avijit Paul, Asmita Samadder, Soumya Sundar Bhattacharyya, Anisur Rahman Khuda-Bukhsh

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

Activation of signal transducer and activator of transcription3 (STAT3) is a hallmark of several types of cancer. Failure to inhibit STAT3 expression by injection of siRNA for STAT3 directly to Balb/c mice led us to adopt alternative means. We formulated nanoparticle-based encapsulation of siRNA (NsiRNA) with polyethylenimine (PEI) and poly(lactide co-glycolide) (PLGA) and characterized them. The siRNA treated and NsiRNA-treated cells were subjected separately to different assay systems. We also checked if NsiRNA could cross the blood brain barrier (BBB). Cell viability reduced dramatically in A549 cells after NsiRNA administration (23.89% at 24. h), thereby implicating considerable silencing of STAT3 by NsiRNA, but not after siRNA administration. Compared to controls, a significant decrease in expression of IL-6 and the angiogenic factor (VEGF) and increase in Caspase 3 activity was observed with corresponding regression in tumor growth in mice treated with NsiRNA. NsiRNA induced apoptosis of cells and arrested cells at G1/G0 stage, both in vitro and in vivo. Apoptosis was also verified by Annexin-V-FITC/Propidium-iodide staining. NsiRNA could cross blood brain barrier. Overall results revealed PEI-PLGA to be a promising carrier for delivery of siRNA targeting STAT3 expression, which can be utilized as an effective strategy for cancer therapy.

Original languageEnglish
Pages (from-to)454-466
Number of pages13
JournalToxicology Letters
Volume225
Issue number3
DOIs
StatePublished - 21 Mar 2014
Externally publishedYes

Keywords

  • Blood brain barrier
  • Drug delivery
  • Lung cancer
  • Mice
  • STAT3 siRNA nanoparticle

ASJC Scopus subject areas

  • Toxicology

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