Minimizing the potential of cancer recurrence and metastasis by the use of graphene oxide nano-flakes released from smart fiducials during image-guided radiation therapy |
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| Institution: | 1. Department of Radiation Oncology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA;2. Department of Radiation Oncology, University of Washington Medical Center, Seattle, WA, USA;3. Medical Physics Program, Department of Physics and Applied Physics, University of Massachusetts, Lowell, MA, USA;4. National Physical Laboratory, Delhi, India;5. Division of Biological & Life Sciences, Ahmedabad University, Ahmedabad, India;6. Nanomedicine Science and Technology Center, Northeastern University, USA;1. Digital Medical Research Center, School of Basic Medical Sciences, Fudan University, Shanghai, China;2. Shanghai Key Laboratory of Medical Imaging Computing and Computer Assisted Intervention, Shanghai, China;1. Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennslyvania;2. Department of Radiation Oncology, University of Maryland Medical Center, Baltimore, Maryland;3. Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas;1. Department of Thoracic Surgery, Tokyo Medical University, Tokyo, Japan;2. Department of Chest Surgery, St Marianna University School of Medicine, Kanagawa, Japan;3. Department of Anatomic Pathology, Tokyo Medical University, Tokyo, Japan;1. Health Physics Unit, ASST Santi Paolo e Carlo, ASST Santi Paolo e Carlo, Milan, Italy;2. Nuclear Medicine Unit, Department of Health Sciences, ASST Santi Paolo e Carlo, University of Milan, Milan, Italy;3. Department of Medical Physics, University Hospital “Maggiore della Carità”, Novara, Italy;1. Università degli Studi di Palermo, Dipartimento di Fisica e Chimica, Viale delle Scienze Ed. 18, 90128 Palermo, Italy;2. A.R.N.A.S. Civico Di Cristina Benfratelli, U.O.C. Fisica Sanitaria, Piazza Nicola Leotta 4, 90127 Palermo, Italy |
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| Abstract: | An increasing number of studies show that cancer stem cells become more invasive and may escape into blood stream and lymph nodes before they have received a lethal dose during radiation therapy. Recently, it has been found that graphene oxide (GO) can selectively inhibit the proliferative expansion of cancer stem cells across multiple tumor types. In this study, we investigate the feasibility of using GO during radiotherapy to synergistically inhibit cancer stem cells, and lower the risk of cancer metastasis and recurrence. We hypothesize that graphene oxide nano-flakes (GONFs) released from newly-designed radiotherapy biomaterials (fiducial) can reach targeted tumor cells within 14–21 days. These are the typical time periods between the implantation of the fiducial and the start of image-guided radiation therapy. To test this hypothesis, the spatial-temporal diffusion of GONFs in soft tissue is investigated as a function of different particle sizes. Toxicity of GONFs to normal (HUVEC) and cancer (A549) cells has been assessed using the MTT assay. In addition, the survival fraction of A549 cells treated with GONFs is determined via clonogenic assay during radiotherapy. The diffusion study shows that only GONFs sizes of 50 and 200 nm could achieve the desired concentration of 50 μg/mL for 2 cm diameter tumor after 14 and 21 days respectively. The clonogenic and the MTT assay confirm the additional benefit of GONFs in killing lung cancer cells during radiotherapy. This work avails ongoing in vivo studies that use GONFs to enhance the treatment outcome for cancer patients during radiation therapy. |
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| Keywords: | Graphene oxide Nano-flakes Cancer stem cell IGRT Cancer recurrence Cancer metastasis |
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