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1.
Nanomedicine ; 12(3): 611-621, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26656626

RESUMO

Superparamagnetic iron-oxide based contrast agents can provide important diagnostic information regarding the assessment of cardiac inflammatory diseases. The aim of the study was to analyze whether nanoparticles conjugated to recombinant 70-kDa heat shock protein (Hsp70-SPION) can be applied for the detection of acute myocardium infarct by MRI. Cellular experiments demonstrated increased CD40-mediated uptake of Hsp70-SPIONs in comparison to non-conjugated SPIONs. Following induction of an acute infarct in rats by ligation of the left anterior descending artery SPIONs and Hsp70-SPION conjugates were injected intravenously on day 4. The animals underwent sequential MRI that showed the presence of the particles in the infarcted zone. Subsequent biodistribution analyses with the help of method on non-linear magnetic response indicated the preferential accumulation of the Hsp70-SPIONs in the heart tissue that was further confirmed with histological analyses. The study demonstrated that an acute infarct can be visualized by MRI using Hsp70-functionalized SPION conjugates. FROM THE CLINICAL EDITOR: Superparamagnetic iron oxides nanoparticles (SPIONs) have been studied extensively as a contrast agent for MRI. Their tissue specificity can be further enhanced by conjugation with various ligands. In this study, the authors conjugated superparamagnetic nanoparticles to 70-kDa heat shock protein (Hsp70-SPION) to investigate the feasibility for the detection of acute myocardium infarct. The positive findings would suggest that this approach might be used clinically in the future.


Assuntos
Meios de Contraste/química , Compostos Férricos/química , Proteínas de Choque Térmico HSP70/química , Imageamento por Ressonância Magnética/métodos , Nanopartículas de Magnetita/química , Infarto do Miocárdio/diagnóstico por imagem , Animais , Meios de Contraste/farmacocinética , Compostos Férricos/farmacocinética , Proteínas de Choque Térmico HSP70/farmacocinética , Nanopartículas de Magnetita/análise , Masculino , Miocárdio/patologia , Ratos Wistar , Distribuição Tecidual
2.
Nanoscale ; 7(48): 20652-64, 2015 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-26599206

RESUMO

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.


Assuntos
Anticorpos Monoclonais Murinos , Neoplasias Encefálicas/terapia , Quimiorradioterapia/métodos , Sistemas de Liberação de Medicamentos/métodos , Raios gama/uso terapêutico , Glioma/terapia , Proteínas de Choque Térmico HSP70/antagonistas & inibidores , Nanopartículas de Magnetita/química , Animais , Anticorpos Monoclonais Murinos/química , Anticorpos Monoclonais Murinos/farmacologia , Proteínas de Choque Térmico HSP70/química , Células HeLa , Humanos , Células K562 , Masculino , Ratos , Ratos Wistar
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