Journal
SMALL
Volume 15, Issue 13, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/smll.201900205
Keywords
glioblastoma; granzyme B; magnetic targeting; radiotherapy; superparamagnetic nanoparticles
Categories
Funding
- Alexander von Humboldt Fellowship
- BMBF Innovative therapies [01GU0823]
- BMBF Kompetenzverbund Strahlenforschung [02NUK038A0]
- BMWi (AiF project) [ZF4320102CS7]
- DFG, Germany [SFB824/3]
- DFG [STA1520/1-1]
- Technische Universitat Munchen (TUM) within the DFG funding programme Open Access Publishing
- British Council Institutional Links grant, under the Russia-UK partnership [ID 277386067]
- Russian Foundation for Basic Research (RFBR) [19-08-00024]
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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.
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