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Development of Fe3O4 coreā€“TiO2 shell nanocomposites and nanoconjugates as a foundation for neuroblastoma radiosensitization

DOI: 10.1186/s12645-021-00081-z DOI Help

Authors: William Liu (Northwestern University) , Salida Mirzoeva (Northwestern University) , Ye Yuan (Northwestern University) , Junjing Deng (Northwestern University) , Si Chen (Argonne National Laboratory) , Barry Lai (Argonne National Laboratory) , Stefan Vogt (Argonne National Laboratory) , Karna Shah (Northwestern University) , Rahul Shroff (Northwestern University) , Reiner Bleher (Northwestern University) , Qiaoling Jin (Northwestern University) , Nghia Vo (Diamond Light Source) , Remon Bazak (University of Alexandria) , Carissa Ritner (Northwestern University) , Stanley Gutionov (Northwestern University) , Sumita Raha (Northwestern University) , Julia Sedlmair (Synchrotron Radiation Center) , Carol Hirschmugl (Synchrotron Radiation Center; University of Wisconsin-Milwaukee) , Chris Jacobsen (Northwestern University; Argonne National Laboratory) , Tatjana Paunesku (Northwestern University) , John Kalapurkal (Northwestern University) , Gayle E. Woloschak (Northwestern University)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Cancer Nanotechnology , VOL 12

State: Published (Approved)
Published: May 2021

Open Access Open Access

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 excit- ing and unexploited opportunities to overcome the shortcomings of conventional medicine. The photocatalytic properties of Fe O core-TiO shell nanocomposites and 3 4 2 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 radiosensitiz- ers 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 nanoconju- gates 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 radiosensitiza- tion 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.

Journal Keywords: Nanocomposites; Nanoconjugates; Iron oxide core nanoparticles; Titanium dioxide shell nanoparticles; Neuroblastoma; Radiosensitization

Diamond Keywords: Neuroblastoma

Subject Areas: Biology and Bio-materials, Materials, Medicine

Facility: 2-ID-D, 2-ID-E, and LS-CAT 21-ID-D Bionanoprobe at Advanced Photon Source

Added On: 26/05/2021 10:23


Discipline Tags:

Non-Communicable Diseases Health & Wellbeing Cancer Biochemistry Chemistry Materials Science Inorganic Chemistry Nanoscience/Nanotechnology Life Sciences & Biotech

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