PLK1 and EGFR targeted nanoparticle as a radiation sensitizer for non-small cell lung cancer

Moataz Reda, Worapol Ngamcherdtrakul, Shenda Gu, Daniel S. Bejan, Natnaree Siriwon, Joe W. Gray, Wassana Yantasee

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Radiation sensitizers that can selectively act on cancer cells hold great promise to patients who receive radiation therapy. We developed a novel targeted therapy and radiation sensitizer for non-small cell lung cancer (NSCLC) based on cetuximab conjugated nanoparticle that targets epidermal growth factor receptor (EGFR) and delivers small interfering RNA (siRNA) against polo-like kinase 1 (PLK1). EGFR is overexpressed in 50% of lung cancer patients and a mediator of DNA repair, while PLK1 is a key mitotic regulator whose inhibition enhances radiation sensitivity. The nanoparticle construct (C-siPLK1-NP) effectively targets EGFR + NSCLC cells and reduces PLK1 expression, leading to G2/M arrest and cell death. Furthermore, we show a synergistic combination between C-siPLK1-NP and radiation, which was confirmed in vivo in A549 flank tumors. We also demonstrate the translational potential of C-siPLK1-NP as a systemic therapeutic in an orthotopic lung tumor model, where administration of C-siPLK1-NP reduced tumor growth and led to prolonged survival. Our findings demonstrate that C-siPLK1-NP is effective as a targeted therapy and as a potent radiation sensitizer for NSCLC. Potential application to other EGFR + cancer types such as colorectal and breast cancer is also demonstrated.

Original languageEnglish (US)
Pages (from-to)9-18
Number of pages10
JournalCancer Letters
Volume467
DOIs
StatePublished - Dec 28 2019

Keywords

  • Epidermal growth factor receptor
  • Mesoporous silica
  • Polo-like kinase
  • Radiosensitizer
  • Small interfering RNA (siRNA)

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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