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

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

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Radiation-Sensitizing Agents
Epidermal Growth Factor Receptor
Non-Small Cell Lung Carcinoma
Nanoparticles
Neoplasms
Radiation Tolerance
DNA Repair
Small Interfering RNA
Colorectal Neoplasms
Lung Neoplasms
Cell Death
Radiotherapy
Therapeutics
polo-like kinase 1
Radiation
Breast Neoplasms
Lung
Survival
Growth

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

PLK1 and EGFR targeted nanoparticle as a radiation sensitizer for non-small cell lung cancer. / Reda, Moataz; Ngamcherdtrakul, Worapol; Gu, Shenda; Bejan, Daniel S.; Siriwon, Natnaree; Gray, Joe W.; Yantasee, Wassana.

In: Cancer Letters, Vol. 467, 28.12.2019, p. 9-18.

Research output: Contribution to journalArticle

Reda, Moataz ; Ngamcherdtrakul, Worapol ; Gu, Shenda ; Bejan, Daniel S. ; Siriwon, Natnaree ; Gray, Joe W. ; Yantasee, Wassana. / PLK1 and EGFR targeted nanoparticle as a radiation sensitizer for non-small cell lung cancer. In: Cancer Letters. 2019 ; Vol. 467. pp. 9-18.
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