Milad Enferadi1, Sheng-Yung Fu2,3, Ji-Hong Hong3,4, Chuan-Jong Tung1,5, Tsi-Chian Chao1,5, Shiaw-Pyng Wey1, Chun-Hui Chiu6, Chun-Chieh Wang3, Mahdi Sadeghi7. 1. a Department of Medical Imaging and Radiological Sciences, College of Medicine , Chang Gung University , Tao-yuan , Taiwan. 2. b Department of Biomedical Engineering and Environmental Sciences , National Tsing Hua University , Hsinchu , Taiwan. 3. c Department of Radiation Oncology , Chang Gung Memorial Hospital , Tao-Yuan , Taiwan. 4. d Radiation Biology Research Center, Institute for Radiological Research , Chang Gung University/Chang Gung Memorial Hospital , Tao-Yuan , Taiwan. 5. e Medical Physics Research Center, Institute for Radiological Research , Chang Gung University/Chang Gung Memorial Hospital , Tao-Yuan , Taiwan. 6. f Graduate Institute of Health-Industry Technology, Research Center for Food and Cosmetic Safety, College of Human Ecology , Chang Gung University of Science and Technology , Tao-Yuan , Taiwan. 7. g Medical Physics Department, School of Medicine , Iran University of Medical Science , Tehran , Iran.
Abstract
PURPOSE: One of the promising radiosensitizers is the ultrasmall gold nanoparticle (GNP) with a hydrodynamic diameter <3 nm. We studied functionalized ultrasmall GNPs (1.8 nm diameter) coated by polyethylene glycol (PEG) and conjugated with cyclic RGDfK (2.6 nm hydrodynamic diameter) for targeting of alpha(v) beta(3) integrin (αvβ3) in the murine ALTS1C1 glioma cell line. MATERIALS AND METHODS: We investigated the uptake, toxicity and radiosensitivity of GNP-PEG-cRGDfKs in ALTS1C1 cells exposed to protons, kilovoltage photons and megavoltage photons. The in vitro uptake and toxicity of GNPs in the hepatocytes and Kupffer cells were assessed for murine AML12 hepatocyte and RAW 264.7 macrophage cell lines. The in vivo biodistribution of GNPs in the ALTS1C1 tumor model was tested using the inductively coupled plasma mass spectrometry. RESULTS: Results indicated GNPs accumulated in the cytoplasm with negligible toxicity for a moderate concentration of GNPs. Observed sensitizer enhancement ratios and dose enhancement factors are 1.21-1.66 and 1.14-1.33, respectively, for all radiations. CONCLUSION: Ultrasmall GNP-PEG-cRGD can be considered as a radiosensitizer. For radiotherapy applications, the delivery method should be developed to increase the GNP uptake in the tumor and decrease the uptakes in undesirable organs.
PURPOSE: One of the promising radiosensitizers is the ultrasmall gold nanoparticle (GNP) with a hydrodynamic diameter <3 nm. We studied functionalized ultrasmall GNPs (1.8 nm diameter) coated by polyethylene glycol (PEG) and conjugated with cyclic RGDfK (2.6 nm hydrodynamic diameter) for targeting of alpha(v) beta(3) integrin (αvβ3) in the murine ALTS1C1 glioma cell line. MATERIALS AND METHODS: We investigated the uptake, toxicity and radiosensitivity of GNP-PEG-cRGDfKs in ALTS1C1 cells exposed to protons, kilovoltage photons and megavoltage photons. The in vitro uptake and toxicity of GNPs in the hepatocytes and Kupffer cells were assessed for murine AML12 hepatocyte and RAW 264.7 macrophage cell lines. The in vivo biodistribution of GNPs in the ALTS1C1 tumor model was tested using the inductively coupled plasma mass spectrometry. RESULTS: Results indicated GNPs accumulated in the cytoplasm with negligible toxicity for a moderate concentration of GNPs. Observed sensitizer enhancement ratios and dose enhancement factors are 1.21-1.66 and 1.14-1.33, respectively, for all radiations. CONCLUSION: Ultrasmall GNP-PEG-cRGD can be considered as a radiosensitizer. For radiotherapy applications, the delivery method should be developed to increase the GNP uptake in the tumor and decrease the uptakes in undesirable organs.
Authors: Maria A Kolyvanova; Alexandr V Belousov; Grigorii A Krusanov; Alexandra K Isagulieva; Kirill V Morozov; Maria E Kartseva; Magomet H Salpagarov; Pavel V Krivoshapkin; Olga V Dement'eva; Victor M Rudoy; Vladimir N Morozov Journal: Int J Mol Sci Date: 2021-06-02 Impact factor: 5.923