Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Gold Nanoparticle Mediated Multi-Modal CT Imaging of 3 Hsp70 Membrane Positive Tumors

Version 1 : Received: 16 April 2020 / Approved: 17 April 2020 / Online: 17 April 2020 (08:42:18 CEST)

A peer-reviewed article of this Preprint also exists.

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. 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.

Journal reference: Cancers 2020, 12, 1331
DOI: 10.3390/cancers12051331

Abstract

Imaging techniques such as computed tomographies (CT) play a major role in clinical imaging and diagnosis of malignant lesions. In recent years, spectral CT has emerged in the field of computed tomographies, utilizing detailed information from extracted spectral parameters of the specimen. Metal nanoparticle platforms enable effective payload delivery for this technique. 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 functionalized gold nanoparticles (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 tissue cells, predestining this target epitope for tumor-selective in vivo targeting. In vitro microscopical analysis revealed the presence of cmHsp70.1-AuNP in the cytosol of tumor cell lines, being internalized via the endosomal-lysosomal pathway. In tumor bearing mice the biodistribution as well as the intratumorally enrichment of AuNP were examined 24h after i.v. application, in vivo. In parallel to spectral CT analysis, histological analysis confirmed the presence of tumor cells. In contrast to control NP, a significant enrichment of cmHsp70.1-AuNPs has been detected selectively in tumors of different preclinical mouse models. Furthermore, the biodistribution of AuNP, following i.v. injection, was analyzed by a machine-learning approach on digitalized slides. In summary, utilizing mHsp70 on tumor cells for guidance of cmHsp70.1 antibody functionalized nanoparticles enables sufficient enrichment and uniform distribution of AuNPs in mHsp70-expressing tumor cells, adequate for various microscopical imaging techniques and spectral-CT-based tumor delineation, in vivo.

Subject Areas

gold nanoparticle; heat shock protein 70; molecular imaging; biomarker; spectral-CT; k-edge imaging

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