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Theranostic nanoparticles enhance the response of glioblastomas to radiation
Wu, W. Klockow, J.L. Mohanty, S. Ku, K.S. Aghighi, M. Melemenidis, S. Chen, Z. Li, K. Ribeiro Morais, Goreti Zhao, N.
Wu, W.
Klockow, J.L.
Mohanty, S.
Ku, K.S.
Aghighi, M.
Melemenidis, S.
Chen, Z.
Li, K.
Ribeiro Morais, Goreti
Zhao, N.
Publication Date
2019-09-17
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(c) 2019 The Authors. This is an Open Access article distributed under the terms of the Creative Commons CC-BY license (https://creativecommons.org/licenses/by/4.0/)
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openAccess
Accepted for publication
2019-09-14
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Abstract
Despite considerable progress with our understanding of glioblastoma multiforme (GBM) and the precise
delivery of radiotherapy, the prognosis for GBM patients is still unfavorable with tumor recurrence due
to radioresistance being a major concern. We recently developed a cross-linked iron oxide nanoparticle
conjugated to azademethylcolchicine (CLIO-ICT) to target and eradicate a subpopulation of quiescent
cells, glioblastoma initiating cells (GICs), which could be a reason for radioresistance and tumor relapse.
The purpose of our study was to investigate if CLIO-ICT has an additive therapeutic effect to enhance the
response of GBMs to ionizing radiation.
Methods: NSG™ mice bearing human GBMs and C57BL/6J mice bearing murine GBMs received
CLIO-ICT, radiation, or combination treatment. The mice underwent pre- and post-treatment magnetic
resonance imaging (MRI) scans, bioluminescence imaging (BLI), and histological analysis. Tumor
nanoparticle enhancement, tumor flux, microvessel density, GIC, and apoptosis markers were compared
between different groups using a one-way ANOVA and two-tailed Mann-Whitney test. Additional NSG™
mice underwent survival analyses with Kaplan–Meier curves and a log rank (Mantel–Cox) test.
Results: At 2 weeks post-treatment, BLI and MRI scans revealed significant reduction in tumor size for
CLIO-ICT plus radiation treated tumors compared to monotherapy or vehicle-treated tumors.
Combining CLIO-ICT with radiation therapy significantly decreased microvessel density, decreased
GICs, increased caspase-3 expression, and prolonged the survival of GBM-bearing mice. CLIO-ICT
delivery to GBM could be monitored with MRI. and was not significantly different before and after
radiation. There was no significant caspase-3 expression in normal brain at therapeutic doses of
CLIO-ICT administered.
Conclusion: Our data shows additive anti-tumor effects of CLIO-ICT nanoparticles in combination with
radiotherapy. The combination therapy proposed here could potentially be a clinically translatable
strategy for treating GBMs.
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Citation
Wu W, Klockow JL, Mohanty S et al (2019) Theranostic nanoparticles enhance the response of glioblastomas to radiation. Nanotheranostics. 3(1): 299-310.
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Article