Irradiation of cancer cells by non‐ionizing millimeter waves (MMW) causes increased cell mortality. We examined if MMW have toxic effects on healthy mice. To that end, the skin of healthy C57BL/6 mice was irradiated locally at the right flank with 101 GHz MMW in a pulsed (5–10 µs) regime using a free electron laser. Irradiation was performed in a dose‐dependent manner, with 20–50 pulses and a power range of 0.5–1.5 kW. Physical, physiological, and pathological parameters as well as behavior were examined before and after irradiation. Our results showed that all parameters were within normal range for all experimental mice groups and for the control group. No significant changes were noted in the physical, physiological, or behavioral status of the mice following irradiation as compared with the control group. In addition, no significant changes were found in locomotor, exploratory behavior, or anxiety of the irradiated mice and no pathological changes were noted following the hematological and biochemical blood analysis. Our results indicate that irradiation of healthy mice with MMW does not cause any general toxic effects. Bioelectromagnetics. © 2020 Bioelectromagnetics Society.

The epidermal growth factor–epidermal growth factor receptor (EGF-EGFR) pathway has become the main focus of selective chemotherapeutic intervention. As a result, two classes of EGFR inhibitors have been clinically approved, namely monoclonal antibodies and small molecule kinase inhibitors. Despite an initial good response rate to these drugs, most patients develop drug resistance. Therefore, new treatment approaches are needed. In this work, we aimed to find a new EGFR-specific, short cyclic peptide, which could be used for targeted drug delivery. Phage display peptide technology and biopanning were applied to three EGFR expressing cells, including cells expressing the EGFRvIII mutation. DNA from the internalized phage was extracted and the peptide inserts were sequenced using next-generation sequencing (NGS). Eleven peptides were selected for further investigation using binding, internalization, and competition assays, and the results were confirmed by confocal microscopy and peptide docking. Among these eleven peptides, seven showed specific and selective binding and internalization into EGFR positive (EGFR+ve) cells, with two of them—P6 and P9—also demonstrating high specificity for non-small cell lung cancer (NSCLC) and glioblastoma cells, respectively. These peptides were chemically conjugated to camptothecin (CPT). The conjugates were more cytotoxic to EGFR+ve cells than free CPT. Our results describe a novel cyclic peptide, which can be used for targeted drug delivery to cells overexpressing the EGFR and EGFRvIII mutation.

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