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

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

Research output: Contribution to journal › Article › peer-review

39 Scopus citations

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.

Original language	English
Article number	1900205
Journal	Small
Volume	15
Issue number	13
DOIs	https://doi.org/10.1002/smll.201900205
State	Published - 27 Mar 2019
Externally published	Yes

Keywords

glioblastoma
granzyme B
magnetic targeting
radiotherapy
superparamagnetic nanoparticles

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/smll.201900205

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Shevtsov, M., Stangl, S., Nikolaev, B., Yakovleva, L., Marchenko, Y., Tagaeva, R., Sievert, W., Pitkin, E., Mazur, A., Tolstoy, P., Galibin, O., Ryzhov, V., Steiger, K., Smirnov, O., Khachatryan, W., Chester, K., & Multhoff, G. (2019). Granzyme B Functionalized Nanoparticles Targeting Membrane Hsp70-Positive Tumors for Multimodal Cancer Theranostics. Small, 15(13), Article 1900205. https://doi.org/10.1002/smll.201900205

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title = "Granzyme B Functionalized Nanoparticles Targeting Membrane Hsp70-Positive Tumors for Multimodal Cancer Theranostics",

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.",

keywords = "glioblastoma, granzyme B, magnetic targeting, radiotherapy, superparamagnetic nanoparticles",

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

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Shevtsov, M, Stangl, S, Nikolaev, B, Yakovleva, L, Marchenko, Y, Tagaeva, R, Sievert, W, Pitkin, E, Mazur, A, Tolstoy, P, Galibin, O, Ryzhov, V, Steiger, K, Smirnov, O, Khachatryan, W, Chester, K & Multhoff, G 2019, 'Granzyme B Functionalized Nanoparticles Targeting Membrane Hsp70-Positive Tumors for Multimodal Cancer Theranostics', Small, vol. 15, no. 13, 1900205. https://doi.org/10.1002/smll.201900205

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AU - Shevtsov, Maxim

AU - Stangl, Stefan

AU - Nikolaev, Boris

AU - Yakovleva, Ludmila

AU - Marchenko, Yaroslav

AU - Tagaeva, Ruslana

AU - Sievert, Wolfgang

AU - Pitkin, Emil

AU - Mazur, Anton

AU - Tolstoy, Peter

AU - Galibin, Oleg

AU - Ryzhov, Vyacheslav

AU - Steiger, Katja

AU - Smirnov, Oleg

AU - Khachatryan, William

AU - Chester, Kerry

AU - Multhoff, Gabriele

PY - 2019/3/27

Y1 - 2019/3/27

N2 - 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.

AB - 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.

KW - glioblastoma

KW - granzyme B

KW - magnetic targeting

KW - radiotherapy

KW - superparamagnetic nanoparticles

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JF - Small

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ER -

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

Abstract

Keywords

UN SDGs

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