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Granzyme B Functionalized Nanoparticles Targeting Membrane Hsp70‐Positive Tumors for Multimodal Cancer Theranostics
Author(s) -
Shevtsov Maxim,
Stangl Stefan,
Nikolaev Boris,
Yakovleva Ludmila,
Marchenko Yaroslav,
Tagaeva Ruslana,
Sievert Wolfgang,
Pitkin Emil,
Mazur Anton,
Tolstoy Peter,
Galibin Oleg,
Ryzhov Vyacheslav,
Steiger Katja,
Smirnov Oleg,
Khachatryan William,
Chester Kerry,
Multhoff Gabriele
Publication year - 2019
Publication title -
small
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.785
H-Index - 236
eISSN - 1613-6829
pISSN - 1613-6810
DOI - 10.1002/smll.201900205
Subject(s) - granzyme b , granzyme , cancer research , cancer cell , chemistry , perforin , cytotoxic t cell , materials science , cancer , biology , biochemistry , in vitro , genetics
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.