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Gaca, S.* ; Reichert, S.* ; Multhoff, G. ; Wacker, M.* ; Hehlgans, S.* ; Botzler, C.* ; Gehrmann, M.* ; Rödel, C.* ; Kreuter, J.* ; Rödel, F.*

Targeting by cmHsp70.1-antibody coated and survivin miRNA plasmid loaded nanoparticles to radiosensitize glioblastoma cells.

J. Control. Release 172, 201-206 (2013)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Nanoparticles (NP) as carriers for anti-cancer drugs have shown great promise. Specific targeting of NP to malignant cells, however, remains an unsolved problem. Conjugation of antibodies specific for tumor membrane antigens to NP represents one approach to improve specificity and to increase therapeutic efficacy. In the present study, for the first time a novel membrane heat shock protein (Hsp70)-specific antibody (cmHsp70.1) was coupled to human serum albumin (HSA) NP, loaded with microRNA (miRNA) plasmids to target the inhibitor of apoptosis protein survivin. The physicochemical properties of monodisperse miRNA-loaded NP showed a diameter of 180nm to 220nm, a plasmid incorporation of more than 95% and a surface binding capacity of the antibody of 70-80%. Antibody-conjugated NP displayed an increased cellular uptake in U87MG and LN229 glioblastoma cells compared to isotype control antibody, PEG-coupled controls and peripheral blood lymphocytes (PBL). Survivin expression was significantly reduced in cells treated with the Hsp70-miRNA-NP as compared to non-conjugated NP. Hsp70-miRNA-NP enhanced radiation-induced increase in caspase 3/7 activity and decrease in clonogenic cell survival. In summary, cmHsp70.1 miRNA-NP comprise an enhanced tumor cell uptake and increased therapeutic efficacy of radiation therapy in vitro and provide the basis for the development of antibody-based advanced carrier systems for a tumor cell specific targeting.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords HSA nanoparticles; Expression plasmids; RNA interference; Survivin; Radiosensitization; Glioblastoma; Serum-albumin Nanoparticles; Blood-brain-barrier; Breast-cancer Cells; Heat-shock-protein-70 Hsp70; Stress-proteins; Drug Discovery; Radiotherapy; Expression; Antibody; Radioresistance
ISSN (print) / ISBN 0168-3659
e-ISSN 1873-4995
Journal Journal of Controlled Release
Quellenangaben Volume: 172, Issue: 1, Pages: 201-206 Article Number: , Supplement: ,
Publisher Elsevier
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) CCG Innate Immunity in Tumor Biology (IBMI-KTB)