Development of Fe3O4 core–TiO2 shell nanocomposites and nanoconjugates as a foundation for neuroblastoma radiosensitization

Cancer Nanotechnology

Reiner Bleher¹  Remon Bazak²  Junjing Deng³  Qiaoling Jin³  Chris Jacobsen⁴  Rahul Shroff⁵  William Liu⁵  Karna Shah⁵  Ye Yuan⁵  Gayle E. Woloschak⁵  Tatjana Paunesku⁵  Carissa Ritner⁵  John Kalapurkal⁵  Stanley Gutionov⁵  Salida Mirzoeva⁵  Sumita Raha⁵  Nghia Vo⁶  Julia Sedlmair⁷  Carol Hirschmugl⁸  Stefan Vogt⁹  Barry Lai⁹  Si Chen⁹ 

[1] Chemistry of Life Processes Institute, Northwestern University, 60208, Evanston, IL, USA;Department of Otorhinolaryngology, Faculty of Medicine, University of Alexandria, Alexandria, Egypt;Department of Physics and Astronomy, Northwestern University, 60208, Evanston, IL, USA;Department of Physics and Astronomy, Northwestern University, 60208, Evanston, IL, USA;X-Ray Science Division, Argonne National Laboratory, 60439, Argonne, IL, USA;Department of Radiation Oncology, Northwestern University, 60611, Chicago, IL, USA;Diamond Light Source Ltd, Harwell Science and Innovation Campus, OX11 0DE, Didcot, UK;Synchrotron Radiation Center, 3731 Schneider Drive, 53589-3097, Stoughton, WI, USA;Synchrotron Radiation Center, 3731 Schneider Drive, 53589-3097, Stoughton, WI, USA;Physics Department, University of Wisconsin-Milwaukee, 53211, Milwaukee, WI, USA;X-Ray Science Division, Argonne National Laboratory, 60439, Argonne, IL, USA;

关键词: Nanocomposites;    Nanoconjugates;    Iron oxide core nanoparticles;    Titanium dioxide shell nanoparticles;    Neuroblastoma;    Radiosensitization;   

DOI  :  10.1186/s12645-021-00081-z

来源: Springer

【 摘 要 】

BackgroundNeuroblastoma is the most common extracranial solid malignancy in childhood which, despite the current progress in radiotherapy and chemotherapy protocols, still has a high mortality rate in high risk tumors. Nanomedicine offers exciting and unexploited opportunities to overcome the shortcomings of conventional medicine. The photocatalytic properties of Fe3O4 core-TiO2 shell nanocomposites and their potential for cell specific targeting suggest that nanoconstructs produced using Fe3O4 core-TiO2 shell nanocomposites could be used to enhance radiation effects in neuroblastoma. In this study, we evaluated bare, metaiodobenzylguanidine (MIBG) and 3,4-Dihydroxyphenylacetic acid (DOPAC) coated Fe3O4@TiO2 as potential radiosensitizers for neuroblastoma in vitro.ResultsThe uptake of bare and MIBG coated nanocomposites modestly sensitized neuroblastoma cells to ionizing radiation. Conversely, cells exposed to DOPAC coated nanocomposites exhibited a five-fold enhanced sensitivity to radiation, increased numbers of radiation induced DNA double-strand breaks, and apoptotic cell death. The addition of a peptide mimic of the epidermal growth factor (EGF) to nanoconjugates coated with MIBG altered their intracellular distribution. Cryo X-ray fluorescence microscopy tomography of frozen hydrated cells treated with these nanoconjugates revealed cytoplasmic as well as nuclear distribution of the nanoconstructs.ConclusionsThe intracellular distribution pattern of different nanoconjugates used in this study was different for different nanoconjugate surface molecules. Cells exposed to DOPAC covered nanoconjugates showed the smallest nanoconjugate uptake, with the most prominent pattern of large intracellular aggregates. Interestingly, cells treated with this nanoconjugate also showed the most pronounced radiosensitization effect in combination with the external beam x-ray irradiation. Further studies are necessary to evaluate mechanistic basis for this increased radiosensitization effect. Preliminary studies with the nanoparticles carrying an EGF mimicking peptide showed that this approach to targeting could perhaps be combined with a different approach to radiosensitization – use of nanoconjugates in combination with the radioactive iodine. Much additional work will be necessary in order to evaluate possible benefits of targeted nanoconjugates carrying radionuclides.Graphic abstract

【 授权许可】

CC BY