Abstract
There has been great interest in identifying the biological substrate for light-cell interaction and their relations to cancer treatment. In this study, a near-infrared (NIR) laser is focused into the nucleus (nNIR) or cytoplasm (cNIR) of a single living cell by a high numerical aperture condenser to dissect the novel role of cell nucleus in mediating NIR effects on mitochondrial dynamics of A549 non-small cell lung cancer cells. Our analysis showed that nNIR, but not cNIR, triggered mitochondrial fission in 10 min. In contrast, the fission/fusion balance of mitochondria directly exposed to cNIR does not change. While the same phenomenon is also triggered by single molecular interactions between epidermal growth factor (EGF) and its receptor EGFR, pharmacological studies with cetuximab, PD153035, and caffeine suggest EGF signaling crosstalk to DNA damaging response to mediate rapid mitochondrial fission as a result of nNIR irradiation. These results suggest that nuclear DNA integrity is a novel biological target for cellular response to NIR.
Highlights
This study has demonstrated that treating cells with conjugated fluorescence nanodiamond (FND)-epidermal growth factor (EGF) have a significant increase effect on the mitochondrial fragmentation count (MFC) compared to either free EGF treated cells and cells treated with FND only and that we have shown that increased concentration of FND may induce cell stress, mitochondrial dysfunction caused by higher concentration of FND [30]
Our data analysis has shown for the first time a significant increase in MFC’s of cells exposed to Nuclear NIR (nNIR)
We targeted nNIR to demonstrate for the first time that nNIR leads to an increase in MFC and since mitochondrial contained nucleic acid [28] and the deoxyribonucleic acid (DNA)
Summary
Current cancer therapy is composed of three major treatment modalities, including surgery, radiation, and chemotherapy [1]. There is a great interest to improve these modalities or to introduce new modalities to increase therapeutic index and to maximize potential benefits and to minimize the associated risk [2]. Phototherapy is one of such promising modality due to its excellent safety profile and successful preclinical and clinical experiences [2,3]. Due to its compatibility with biological tissues, accuracy/sensitivity, and deep penetration into the tissue (>1 cm) [2,3]. Phototherapy is one such promising modality due to its excellent safety profile and successful early clinical experiences. While common cancer therapeutics target subcellular compartments such as the nucleus [4–6], mitochondria [5,7]
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