Granzyme B Functionalized Nanoparticles Targeting Membrane Hsp70‐Positive Tumors for Multimodal Cancer Theranostics

Maxim Shevtsov, Stefan Stangl, Boris Nikolaev, Ludmila Yakovleva, Yaroslav Marchenko, Ruslana Tagaeva, Wolfgang Sievert, Emil Pitkin, Anton Mazur, Peter Tolstoy, Oleg Galibin, Vyacheslav Ryzhov, Katja Steiger, Oleg Smirnov, William Khachatryan, Kerry Chester, Gabriele Multhoff

doi:10.1002/smll.201900205

Granzyme B Functionalized Nanoparticles Targeting Membrane Hsp70‐Positive Tumors for Multimodal Cancer Theranostics

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Maxim Shevtsov

Center for Translational Cancer Research Technische Universität München (TranslaTUM) Radiation Immuno‐Oncology group Klinikum rechts der Isar Einsteinstr. 25 81675 Munich Germany
Stefan Stangl

Center for Translational Cancer Research Technische Universität München (TranslaTUM) Radiation Immuno‐Oncology group Klinikum rechts der Isar Einsteinstr. 25 81675 Munich Germany
Boris Nikolaev

Research Institute of Highly Pure Biopreparations Pudozhskaya str. 12 St. Petersburg 191014 Russia
Ludmila Yakovleva

Research Institute of Highly Pure Biopreparations Pudozhskaya str. 12 St. Petersburg 191014 Russia
Yaroslav Marchenko

Research Institute of Highly Pure Biopreparations Pudozhskaya str. 12 St. Petersburg 191014 Russia
Ruslana Tagaeva

Research Institute of Highly Pure Biopreparations Pudozhskaya str. 12 St. Petersburg 191014 Russia
Wolfgang Sievert

Center for Translational Cancer Research Technische Universität München (TranslaTUM) Radiation Immuno‐Oncology group Klinikum rechts der Isar Einsteinstr. 25 81675 Munich Germany
Emil Pitkin

Wharton School University of Pennsylvania Walnut Street 3730 Philadelphia PA 19104 USA
Anton Mazur

Saint Petersburg State University Universitetskaya nab. 7‐9 St. Petersburg 199034 Russia
Peter Tolstoy

Saint Petersburg State University Universitetskaya nab. 7‐9 St. Petersburg 199034 Russia
Oleg Galibin

First Pavlov State Medical University of St. Petersburg L'va Tolstogo str. 6/8 St. Petersburg 197022 Russia
Vyacheslav Ryzhov

NRC “Kurchatov Institute” Petersburg Nuclear Physics Institute Gatchina 188300 Russia
Katja Steiger

Institute of Pathology Technische Universität München Trogerstr. 18 81675 Munich Germany
Oleg Smirnov

NRC “Kurchatov Institute” Petersburg Nuclear Physics Institute Gatchina 188300 Russia
William Khachatryan

Almazov National Medical Research Centre Russian Polenov Neurosurgical Institute Mayakovskogo str. 12 St. Petersburg 191104 Russia
Kerry Chester

UCL Cancer Institute University College London 72 Huntley Street WC1E 6DD London UK
Gabriele Multhoff

Center for Translational Cancer Research Technische Universität München (TranslaTUM) Radiation Immuno‐Oncology group Klinikum rechts der Isar Einsteinstr. 25 81675 Munich Germany

書誌事項

公開日: 2019-03

権利情報

http://onlinelibrary.wiley.com/termsAndConditions#vor

DOI

10.1002/smll.201900205

公開者: Wiley

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説明

<jats:title>Abstract</jats:title><jats:p>Functionalized superparamagnetic iron oxide nanoparticles (SPIONs) have emerged as potential clinical tools for cancer theranostics. Membrane‐bound 70 kDa heat shock protein (mHsp70) is ubiquitously expressed on the cell membrane of various tumor types but not normal cells and therefore provides a tumor‐specific target. The serine protease granzyme B (GrB) that is produced as an effector molecule by activated T and NK cells has been shown to specifically target mHsp70 on tumor cells. Following binding to Hsp70, GrB is rapidly internalized into tumor cells. Herein, it is demonstrated that GrB functionalized SPIONs act as a contrast enhancement agent for magnetic resonance imaging and induce specific tumor cell apoptosis. Combinatorial regimens employing stereotactic radiotherapy and/or magnetic targeting are found to further enhance the therapeutic efficacy of GrB‐SPIONs in different tumor mouse models.</jats:p>