Selective Photokilling of Human Pancreatic Cancer Cells Using Cetuximab-Targeted Mesoporous Silica Nanoparticles for Delivery of Zinc Phthalocyanine

WOS: 000451641900021PubMed ID: 30355983Background: 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-)-N-29,N-30,N-31,N-32 (ZnPcOBP)-loaded mesoporous silica nanoparticles against pancreatic cancer cells. Results: The quantum yield (Phi(Delta)) 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/cm(2) 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.Ministerio de Economia y CompetitividadSpanish Ministry of Economy & Competitiveness [CTQ2016-78454-C2-1-R]; Scientific and Technological Research Council of Turkey (TUBITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [2214/A]; Ege University, Scientific Research Project (BAP)Ege University [16 NBE 001]; European Social FundsEuropean Social Fund (ESF); SUR del DEC de la Generalitat de Catalunya [2017 FI_B2 00140]This research was funded by Ministerio de Economia y Competitividad (grant number CTQ2016-78454-C2-1-R), the Scientific and Technological Research Council of Turkey (TUBITAK; grant number 2214/A), Ege University, Scientific Research Project (BAP; grant Number: 16 NBE 001), and the European Social Funds and the SUR del DEC de la Generalitat de Catalunya (grant number 2017 FI_B2 00140)