Abstract
Background: 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. Results: 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. Conclusions: 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. Graphic abstract: [Figure not available: see fulltext.]
Original language | English (US) |
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Article number | 12 |
Journal | Cancer Nanotechnology |
Volume | 12 |
Issue number | 1 |
DOIs | |
State | Published - Dec 2021 |
Funding
This work was supported by the NIH grants CA107467, EB002100, GM104530 and U54 CA151880 and U54CA119341 and a generous gift from Make Your Mark Foundation ( http://makeyourmark7.org/ ). WL was supported in part by the Northwestern University Biotechnology Cluster Training Grant. XFM was performed at the Advanced Photon Source at Argonne National Laboratory at XOR beamlines 2-ID-D, 2-ID-E, and LS-CAT 21-ID-D Bionanoprobe; this instrument was obtained through an NIH ARRA S10 grant SP0007167. Work at Argonne National Laboratory was supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences, Contract No. DE-AC02-06CH11357. We also thank Argonne National Laboratory for support under LDRD project 2013-168-N0.
Keywords
- Iron oxide core nanoparticles
- Nanocomposites
- Nanoconjugates
- Neuroblastoma
- Radiosensitization
- Titanium dioxide shell nanoparticles
ASJC Scopus subject areas
- Biomedical Engineering
- Oncology
- Pharmaceutical Science
- Physical and Theoretical Chemistry
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Additional file 2 of Development of Fe3O4 core–TiO2 shell nanocomposites and nanoconjugates as a foundation for neuroblastoma radiosensitization
Liu, W. (Creator), Mirzoeva, S. (Creator), Yuan, Y. (Creator), Deng, J. (Creator), Chen, S. (Creator), Lai, B. (Creator), Vogt, S. (Creator), Shah, K. (Creator), Shroff, R. (Creator), Bleher, R. (Creator), Jin, Q. (Creator), Vo, N. (Creator), Bazak, R. (Creator), Ritner, C. (Creator), Gutionov, S. (Creator), Raha, S. (Creator), Sedlmair, J. (Creator), Hirschmugl, C. (Creator), Jacobsen, C. (Creator), Paunesku, T. (Creator), Kalapurkal, J. (Creator), Woloschak, G. E. (Creator), Blaud, A. (Contributor) & Almeida, A. (Contributor), figshare, 2021
DOI: 10.6084/m9.figshare.14600521, https://springernature.figshare.com/articles/media/Additional_file_2_of_Development_of_Fe3O4_core_TiO2_shell_nanocomposites_and_nanoconjugates_as_a_foundation_for_neuroblastoma_radiosensitization/14600521
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