Selective photokilling of human pancreatic cancer cells using cetuximab-targeted mesoporous silica nanoparticles for delivery of zinc phthalocyanine

Özge Er, Suleyman Gokhan Colak, Kasim Ocakoglu, Mine Ince, Roger Bresolí-Obach, Margarita Mora, Maria Lluïsa Sagristá, Fatma Yurt, Santi Nonell

Research output: Indexed journal article Articlepeer-review

30 Citations (Scopus)

Abstract

Background: Photodynamic therapy (PDT) is a non-invasive and innovative cancer therapy based on the photodynamic effect. In this study, we sought to determine the singlet oxygen production, intracellular uptake, and in vitro photodynamic therapy potential of Cetixumab-targeted, zinc(II) 2,3,9,10,16,17,23,24-octa(tert-butylphenoxy))phthalocyaninato(2-)-N29,N30,N31,N32 (ZnPcOBP)loaded mesoporous silica nanoparticles against pancreatic cancer cells. Results: The quantum yield (Φ) value of ZnPcOBP was found to be 0.60 in toluene. In vitro cellular studies were performed to determine the dark- and phototoxicity of samples with various concentrations of ZnPcOBP by using pancreatic cells (AsPC-1, PANC-1 and MIA PaCa-2) and 20, 30, and 40 J/cm2 light fluences. No dark toxicity was observed for any sample in any cell line. ZnPcOBP alone showed a modest photodynamic activity. However, when incorporated in silica nanoparticles, it showed a relatively high phototoxic effect, which was further enhanced by Cetuximab, a monoclonal antibody that targets the Epidermal Growth Factor Receptor (EGFR). The cell-line dependent photokilling observed correlates well with EGFR expression levels in these cells. Conclusions: Imidazole-capped Cetuximab-targeted mesoporous silica nanoparticles are excellent vehicles for the selective delivery of ZnPcOBP to pancreatic cancer cells expressing the EGFR receptor. The novel nanosystem appears to be a suitable agent for photodynamic therapy of pancreatic tumors.

Original languageEnglish
Article number2749
JournalMolecules
Volume23
Issue number11
DOIs
Publication statusPublished - 24 Oct 2018

Keywords

  • Cetuximab
  • Mesoporous silica nanoparticles
  • Photodynamic therapy
  • Singlet oxygen
  • Zn(II) phthalocyanine

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