Granzyme B Functionalized Nanoparticles Targeting Membrane Hsp70-Positive Tumors for Multimodal Cancer Theranostics.
Granzyme B Functionalized Nanoparticles Targeting Membrane Hsp70-Positive Tumors for Multimodal Cancer Theranostics.
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DOI：
10.1002/smll.201900205
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发表时间：
2019-03
期刊：
影响因子：
13.3
通讯作者：
M. Shevtsov;S. Stangl;B. Nikolaev;L. Yakovleva;Y. Marchenko;R. Tagaeva;W. Sievert;E. Pitkin;
中科院分区：
文献类型：
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作者：
M. Shevtsov;S. Stangl;B. Nikolaev;L. Yakovleva;Y. Marchenko;R. Tagaeva;W. Sievert;E. Pitkin;
功能化的超顺磁性氧化铁纳米颗粒(SPION)已成为癌症治疗的潜在临床工具。膜结合型70 kDa热休克蛋白(MHsp70)广泛表达于多种肿瘤细胞的细胞膜上，而正常细胞则不表达，因此提供了肿瘤特异性靶点。丝氨酸蛋白酶颗粒酶B(GRB)是一种由活化的T细胞和NK细胞产生的效应分子，它能特异性地靶向肿瘤细胞上的mHsp70。在与Hsp70结合后，GRB迅速内化到肿瘤细胞中。在此，证明了GRB功能化的SPION作为磁共振成像的造影剂，并诱导特异性的肿瘤细胞凋亡。采用立体定向放射治疗和/或磁靶向治疗的联合方案被发现在不同的肿瘤小鼠模型中进一步提高了GRB-SPIONS的治疗效果。
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.