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Almstätter, I.* ; Mykhaylyk, O.* ; Settles, M.* ; Altomonte, J.* ; Aichler, M. ; Walch, A.K. ; Rummeny, E.J.* ; Ebert, O.* ; Plank, C.* ; Braren, R.*

Characterization of magnetic viral complexes for targeted delivery in oncology.

Theranostics 5, 667-685 (2015)
Publ. Version/Full Text DOI PMC
Open Access Gold
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Oncolytic viruses are promising new agents in cancer therapy. Success of tumor lysis is often hampered by low intra-tumoral titers due to a strong anti-viral host immune response and insufficient tumor targeting. Previous work on the co-assembly of oncolytic virus particles (VPs) with magnetic nanoparticles (MNPs) was shown to provide shielding from inactivating immune response and improve targeting by external field gradients. In addition, MNPs are detected by magnet resonance imaging (MRI) enabling non-invasive therapy monitoring. In this study two selected core-shell type iron oxide MNPs were assembled with adenovirus (Ad) or vesicular stomatitis virus (VSV). The selected MNPs were characterized by high r2 and r2 (*) relaxivities and thus could be quantified non-invasively by 1.5 and 3.0 tesla MRI with a detection limit below 0.001 mM iron in tissue-mimicking phantoms. Assembly and cell internalization of MNP-VP complexes resulted in 81 - 97 % reduction of r2 and 35 - 82 % increase of r2 (*) compared to free MNPs. The relaxivity changes could be attributed to the clusterization of particles and complexes shown by transmission electron microscopy (TEM). In a proof-of-principle study the non-invasive detection of MNP-VPs by MRI was shown in vivo in an orthotopic rat hepatocellular carcinoma model. In conclusion, MNP assembly and compartmentalization have a major impact on relaxivities, therefore calibration measurements are required for the correct quantification in biodistribution studies. Furthermore, our study provides first evidence of the in vivo applicability of selected MNP-VPs in cancer therapy.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Mri Phantoms ; Mri Relaxivity ; Magnetic Nanoparticles (mnps) ; Magnetic Viral Complexes ; Nanoassembly ; Oncolytic Virus.; Iron-oxide Nanoparticles; Multifocal Hepatocellular-carcinoma; Static Dephasing Regime; Mri Contrast Agents; In-vitro; Labeled Cells; Gene Delivery; Oncolytic Virotherapy; Lentiviral Vectors; Dendritic Cells
Language english
Publication Year 2015
HGF-reported in Year 2015
e-ISSN 1838-7640
Journal Theranostics
Quellenangaben Volume: 5, Issue: 7, Pages: 667-685 Article Number: , Supplement: ,
Publisher Ivyspring
Publishing Place Lake Haven
Reviewing status Peer reviewed
Institute(s) Institute of Pathology (PATH)
Research Unit Analytical Pathology (AAP)
POF-Topic(s) 30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
30205 - Bioengineering and Digital Health
Research field(s) Enabling and Novel Technologies
PSP Element(s) G-500300-001
G-500390-001
PubMed ID 25897333
DOI 10.7150/thno.10438
WOS ID WOS:000353064500002
Scopus ID 84938788368
Erfassungsdatum 2015-04-23
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