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Open AccessArticle

Gold Nanoparticle Mediated Multi-Modal CT Imaging of Hsp70 Membrane-Positive Tumors

1
Department of Diagnostic and Interventional Radiology, Klinikum rechts der Isar der Technischen Universität München, 81675 Munich, Germany
2
Central Institute for Translational Cancer Research (TranslaTUM), Klinikum rechts der Isar der Technischen Universität München, 81675 Munich, Germany
3
Pavlov First Saint Petersburg State Medical University, 197022 St. Petersburg, Russia
4
Institute of Cytology of the Russian Academy of Sciences (RAS), 194064 St. Petersburg, Russia
5
Institute for Advanced Studies, Department of Informatics, Technical University of Munich, 85748 Garching, Germany
6
Philips GmbH Innovative Technologies, Research Laboratories, 22335 Hamburg, Germany
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(5), 1331; https://doi.org/10.3390/cancers12051331
Received: 15 April 2020 / Revised: 18 May 2020 / Accepted: 20 May 2020 / Published: 22 May 2020
(This article belongs to the Special Issue Role of Medical Imaging in Cancers)
Imaging techniques such as computed tomographies (CT) play a major role in clinical imaging and diagnosis of malignant lesions. In recent years, metal nanoparticle platforms enabled effective payload delivery for several imaging techniques. Due to the possibility of surface modification, metal nanoparticles are predestined to facilitate molecular tumor targeting. In this work, we demonstrate the feasibility of anti-plasma membrane Heat shock protein 70 (Hsp70) antibody functionalized gold nanoparticles (cmHsp70.1-AuNPs) for tumor-specific multimodal imaging. Membrane-associated Hsp70 is exclusively presented on the plasma membrane of malignant cells of multiple tumor entities but not on corresponding normal cells, predestining this target for a tumor-selective in vivo imaging. In vitro microscopic analysis revealed the presence of cmHsp70.1-AuNPs in the cytosol of tumor cell lines after internalization via the endo-lysosomal pathway. In preclinical models, the biodistribution as well as the intratumoral enrichment of AuNPs were examined 24 h after i.v. injection in tumor-bearing mice. In parallel to spectral CT analysis, histological analysis confirmed the presence of AuNPs within tumor cells. In contrast to control AuNPs, a significant enrichment of cmHsp70.1-AuNPs has been detected selectively inside tumor cells in different tumor mouse models. Furthermore, a machine-learning approach was developed to analyze AuNP accumulations in tumor tissues and organs. In summary, utilizing mHsp70 on tumor cells as a target for the guidance of cmHsp70.1-AuNPs facilitates an enrichment and uniform distribution of nanoparticles in mHsp70-expressing tumor cells that enables various microscopic imaging techniques and spectral-CT-based tumor delineation in vivo. View Full-Text
Keywords: gold nanoparticle; heat shock protein 70; molecular imaging; biomarker; spectral-CT gold nanoparticle; heat shock protein 70; molecular imaging; biomarker; spectral-CT
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Kimm, M.A.; Shevtsov, M.; Werner, C.; Sievert, W.; Zhiyuan, W.; Schoppe, O.; Menze, B.H.; Rummeny, E.J.; Proksa, R.; Bystrova, O.; Martynova, M.; Multhoff, G.; Stangl, S. Gold Nanoparticle Mediated Multi-Modal CT Imaging of Hsp70 Membrane-Positive Tumors. Cancers 2020, 12, 1331.

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