Journal of Gastrointestinal Surgery

, Volume 21, Issue 1, pp 94–105

Restitution of Tumor Suppressor MicroRNA-145 Using Magnetic Nanoformulation for Pancreatic Cancer Therapy

  • Saini Setua
  • Sheema Khan
  • Murali M. Yallapu
  • Stephen W. Behrman
  • Mohammed Sikander
  • Shabia Shabir Khan
  • Meena Jaggi
  • Subhash C. Chauhan
2016 SSAT Plenary Presentation

DOI: 10.1007/s11605-016-3222-z

Cite this article as:
Setua, S., Khan, S., Yallapu, M.M. et al. J Gastrointest Surg (2017) 21: 94. doi:10.1007/s11605-016-3222-z

Abstract

Introduction

The functional significance of lost microRNAs has been reported in several human malignancies, including pancreatic cancer (PC). Our prior work has identified microRNA-145 (miR-145) as a tumor suppressor microRNA (miRNA) in pancreatic cancer. The restoration of miR-145 downregulates a number of oncogenes including mucin MUC13, a transmembrane glycoprotein that is aberrantly expressed in pancreatic cancer, thus efficiently inhibiting tumor growth in mice. However, lack of an effective tumor-specific delivery system remains an unmet clinical challenge for successful translation of microRNAs.

Methods

We developed a miRNA-145-based magnetic nanoparticle formulation (miR-145-MNPF) and assessed its anti-cancer efficacy. Physico-chemical characterization (dynamic light scattering (DLS), transmission electron microscopy (TEM) and miR-binding efficiency), cellular internalization (Prussian blue and confocal microscopy), miR-145 restitution potential (quantitative reverse-transcription PCR (qRT-PCR), and anti-cancer efficacy (proliferation, colony formation, cell migration, cell invasion assays) of this formulation were performed using clinically relevant pancreatic cancer cell lines (HPAF-II, AsPC-1).

Results

miR-145-MNPF exhibited optimal particle size and zeta potential which effectively internalized and restituted miR-145 in pancreatic cancer cells. miR-145 re-expression resulted in downregulation of MUC13, HER2, pAKT, and inhibition of cell proliferation, clonogenicity, migration, and invasion of pancreatic cancer cells.

Conclusions

miR-145-MNPF is an efficient system for miR-145 delivery and restitution in pancreas cancer that may offer a potential therapeutic treatment for PC either alone or in conjunction with conventional treatment.

Keywords

Magnetic nanoparticlemiR-145Pancreatic cancerTherapeuticsNanotherapies

Copyright information

© The Society for Surgery of the Alimentary Tract 2016

Authors and Affiliations

  • Saini Setua
    • 1
  • Sheema Khan
    • 1
  • Murali M. Yallapu
    • 1
  • Stephen W. Behrman
    • 2
  • Mohammed Sikander
    • 1
  • Shabia Shabir Khan
    • 3
  • Meena Jaggi
    • 1
  • Subhash C. Chauhan
    • 1
  1. 1.Department of Pharmaceutical Sciences and Center for Cancer ResearchUniversity of Tennessee Health Science CenterMemphisUSA
  2. 2.Department of SurgeryUniversity of Tennessee Health Science CenterMemphisUSA
  3. 3.Department of Computer ScienceUniversity of KashmirSrinagarIndia