Ionizing radiation improves glioma-specific targeting of superparamagnetic iron oxide nanoparticles conjugated with cmHsp70.1 monoclonal antibodies (SPION–cmHsp70.1)
| Autor: | Emil Pitkin, Valerij I. Rolich, A. V. Dobrodumov, B. Nikolaev, Y. Marchenko, V. A. Ryzhov, Marina A. Parr, A L Mikhrina, L. Yakovleva, Maxim Shevtsov, Gabriele Multhoff |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Biodistribution Materials science medicine.drug_class Monoclonal antibody Ionizing radiation HeLa Antibodies Monoclonal Murine-Derived Drug Delivery Systems Glioma medicine Animals Humans HSP70 Heat-Shock Proteins General Materials Science Rats Wistar Magnetite Nanoparticles biology Brain Neoplasms Chemoradiotherapy medicine.disease biology.organism_classification Molecular biology In vitro Rats Gamma Rays Monoclonal Cancer research K562 Cells HeLa Cells K562 cells |
| Zdroj: | Nanoscale. 7:20652-20664 |
| ISSN: | 2040-3372 2040-3364 |
| Popis: | The stress-inducible 72 kDa heat shock protein Hsp70 is known to be expressed on the membrane of highly aggressive tumor cells including high-grade gliomas, but not on the corresponding normal cells. Membrane Hsp70 (mHsp70) is rapidly internalized into tumor cells and thus targeting of mHsp70 might provide a promising strategy for theranostics. Superparamagnetic iron oxide nanoparticles (SPIONs) are contrast negative agents that are used for the detection of tumors with MRI. Herein, we conjugated the Hsp70-specific antibody (cmHsp70.1) which is known to recognize mHsp70 to superparamagnetic iron nanoparticles to assess tumor-specific targeting before and after ionizing irradiation. In vitro experiments demonstrated the selectivity of SPION-cmHsp70.1 conjugates to free and mHsp70 in different tumor cell types (C6 glioblastoma, K562 leukemia, HeLa cervix carcinoma) in a dose-dependent manner. High-resolution MRI (11 T) on T(2)-weighted images showed the retention of the conjugates in the C6 glioma model. Accumulation of SPION-cmHsp70.1 nanoparticles in the glioma resulted in a nearly 2-fold drop of T*(2) values in comparison to non-conjugated SPIONs. Biodistribution analysis using NLR-M(2) measurements showed a 7-fold increase in the tumor-to-background (normal brain) uptake ratio of SPION-cmHsp70.1 conjugates in glioma-bearing rats in comparison to SPIONs. This accumulation within Hsp70-positive glioma was further enhanced after a single dose (10 Gy) of ionizing radiation. Elevated accumulation of the magnetic conjugates in the tumor due to radiosensitization proves the combination of radiotherapy and application of Hsp70-targeted agents in brain tumors. |
| Databáze: | OpenAIRE |
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