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

Abstract

Neuroblastoma 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. The 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. The intracellular distribution pattern of different nanoconjugates used in this study was different for different nanoconjugate surface molecules.more » 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.« less

Authors:
 [1];  [1];  [1];  [2];  [3];  [3];  [3];  [1];  [1];  [2];  [2];  [4];  [5];  [1];  [1];  [1];  [6];  [7];  [8];  [1] more »;  [1]; ORCiD logo [1] « less
+ Show Author Affiliations
  1. Northwestern Univ., Chicago, IL (United States)
  2. Northwestern Univ., Evanston, IL (United States)
  3. Argonne National Lab. (ANL), Argonne, IL (United States)
  4. Diamond Light Source Ltd, Didcot (United Kingdom)
  5. Univ. of Alexandria (Egypt)
  6. Synchrotron Radiation Center, Stoughton, WI (United States)
  7. Synchrotron Radiation Center, Stoughton, WI (United States); Univ. of Wisconsin, Milwaukee, WI (United States)
  8. Northwestern Univ., Evanston, IL (United States); Argonne National Lab. (ANL), Argonne, IL (United States)
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES); National Institutes of Health (NIH)
OSTI Identifier:
1840576
Grant/Contract Number:  
AC02-06CH11357
Resource Type:
Accepted Manuscript
Journal Name:
Cancer Nanotechnology
Additional Journal Information:
Journal Volume: 12; Journal Issue: 1; Journal ID: ISSN 1868-6958
Publisher:
BioMed Central
Country of Publication:
United States
Language:
English
Subject:
77 NANOSCIENCE AND NANOTECHNOLOGY; nanocomposites; nanoconjugates; iron oxide core nanoparticles; radiosensitization; titanium dioxide shell nanoparticles

Citation Formats

Liu, William, Mirzoeva, Salida, Yuan, Ye, Deng, Junjing, Chen, Si, Lai, Barry, Vogt, Stefan, Shah, Karna, Shroff, Rahul, Bleher, Reiner, Jin, Qiaoling, Vo, Nghia, Bazak, Remon, Ritner, Carissa, Gutionov, Stanley, Raha, Sumita, Sedlmair, Julia, Hirschmugl, Carol, Jacobsen, Chris, Paunesku, Tatjana, Kalapurkal, John, and Woloschak, Gayle E. Development of Fe3O4 core–TiO2 shell nanocomposites and nanoconjugates as a foundation for neuroblastoma radiosensitization. United States: N. p., 2021. Web. doi:10.1186/s12645-021-00081-z.
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Liu, William, Mirzoeva, Salida, Yuan, Ye, Deng, Junjing, Chen, Si, Lai, Barry, Vogt, Stefan, Shah, Karna, Shroff, Rahul, Bleher, Reiner, Jin, Qiaoling, Vo, Nghia, Bazak, Remon, Ritner, Carissa, Gutionov, Stanley, Raha, Sumita, Sedlmair, Julia, Hirschmugl, Carol, Jacobsen, Chris, Paunesku, Tatjana, Kalapurkal, John, & Woloschak, Gayle E. Development of Fe3O4 core–TiO2 shell nanocomposites and nanoconjugates as a foundation for neuroblastoma radiosensitization. United States. https://doi.org/10.1186/s12645-021-00081-z
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Liu, William, Mirzoeva, Salida, Yuan, Ye, Deng, Junjing, Chen, Si, Lai, Barry, Vogt, Stefan, Shah, Karna, Shroff, Rahul, Bleher, Reiner, Jin, Qiaoling, Vo, Nghia, Bazak, Remon, Ritner, Carissa, Gutionov, Stanley, Raha, Sumita, Sedlmair, Julia, Hirschmugl, Carol, Jacobsen, Chris, Paunesku, Tatjana, Kalapurkal, John, and Woloschak, Gayle E. Fri . "Development of Fe3O4 core–TiO2 shell nanocomposites and nanoconjugates as a foundation for neuroblastoma radiosensitization". United States. https://doi.org/10.1186/s12645-021-00081-z. https://www.osti.gov/servlets/purl/1840576.
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@article{osti_1840576,
title = {Development of Fe3O4 core–TiO2 shell nanocomposites and nanoconjugates as a foundation for neuroblastoma radiosensitization},
author = {Liu, William and Mirzoeva, Salida and Yuan, Ye and Deng, Junjing and Chen, Si and Lai, Barry and Vogt, Stefan and Shah, Karna and Shroff, Rahul and Bleher, Reiner and Jin, Qiaoling and Vo, Nghia and Bazak, Remon and Ritner, Carissa and Gutionov, Stanley and Raha, Sumita and Sedlmair, Julia and Hirschmugl, Carol and Jacobsen, Chris and Paunesku, Tatjana and Kalapurkal, John and Woloschak, Gayle E.},
abstractNote = {Neuroblastoma 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. The 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. The 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.},
doi = {10.1186/s12645-021-00081-z},
journal = {Cancer Nanotechnology},
number = 1,
volume = 12,
place = {United States},
year = {Fri May 14 00:00:00 EDT 2021},
month = {Fri May 14 00:00:00 EDT 2021}
}
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