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

Shevtsov, M; Stangl, S; Nikolaev, B; Yakovleva, L; Marchenko, Y; Tagaeva, R; Sievert, W; ... Multhoff, G; + view all (2019) Granzyme B Functionalized Nanoparticles Targeting Membrane Hsp70‐Positive Tumors for Multimodal Cancer Theranostics. Small , 15 (13) , Article 1900205. 10.1002/smll.201900205. Green open access

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Abstract

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.

Type: Article
Title: Granzyme B Functionalized Nanoparticles Targeting Membrane Hsp70‐Positive Tumors for Multimodal Cancer Theranostics
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/smll.201900205
Publisher version: https://doi.org/10.1002/smll.201900205
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: glioblastoma, granzyme B, magnetic targeting, radiotherapy, superparamagnetic nanoparticles
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
URI: https://discovery.ucl.ac.uk/id/eprint/10091144
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