Abstract
Non-thermal atmospheric pressure plasma (NTP) has been shown to induce cell death in various mammalian cancer cells. Accumulated evidence also shows that NTP could be clinically used in cancer therapy. However, the current NTP-based applications lack target specificity. Here, a novel method in NTP-mediated cancer therapeutics was described with enhanced target specificity by treating EGF (epidermal growth factor)-conjugated GNP (gold nanoparticle). The treatment with EGF-conjugated GNP complex, followed by NTP irradiation showed selective apoptosis of cells having receptor-mediated endocytosis. NTP triggered γ–H2AX elevation which is a typical response elicited by DNA damage. These results suggest that EGF-conjugated GNP functions as an important adjuvant which gives target specificity in applications of conventional plasma therapy.
Highlights
Apoptosis is programmed and orchestrated cell death, and its primary role is to keep cell number homeostasis in multicellular organisms[1,2,3,4]
We hypothesized that receptor-mediated endocytosis of epidermal growth factor (EGF)-gold nanoparticle (GNP) conjugates could target EGF receptor (EGFR)-expressing cells and cause selective apoptosis by subsequent non-thermal atmospheric pressure plasma (NTP) irradiation
We have shown that our EGF-GNP
Summary
Apoptosis is programmed and orchestrated cell death, and its primary role is to keep cell number homeostasis in multicellular organisms[1,2,3,4]. Additional specificity was conferred by using target-specific small molecule inhibitors, monoclonal antibodies, and nucleotides[8, 9] Added to these conventional cancer therapies, Fridman G et al described “plasma medicine” that uses non-thermal atmospheric pressure plasma (NTP) to effectively remove cancer cells as well as to sterilize non-living objects[10]. Kim et al showed that GNP-conjugated antibody against FAK (Focal adhesion kinase) protein effectively targets tumor and increases cell death after NTP irradiation[21]. We report that selective uptake of EGF-GNP complex, followed by NTP treatment efficiently triggered apoptosis. Treatment with NTP induced a significant increase in apoptosis in the EGF-conjugated GNP complex-treated cells. We suggest that the EGF-conjugated GNP complex coupled with NTP treatment efficiently targets EGFR-expressing cancer cells
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