Oncotarget

Research Papers:

The use of a uPAR-targeted probe for photothermal cancer therapy prolongs survival in a xenograft mouse model of glioblastoma

Marina Simón, Jesper Tranekjær Jørgensen, Karina Juhl and Andreas Kjaer _

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Oncotarget. 2021; 12:1366-1376. https://doi.org/10.18632/oncotarget.28013

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Abstract

Marina Simón1, Jesper Tranekjær Jørgensen1, Karina Juhl1 and Andreas Kjaer1

1 Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Department of Biomedical Sciences, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark

Correspondence to:

Andreas Kjaer,email: akjaer@sund.ku.dk

Keywords: photothermal therapy (PTT); indocyanine green (ICG); urokinase plasminogen activator receptor (uPAR); cancer; hyperthermia

Abbreviations: PTT: photothermal therapy; ICG: indocyanine green; NIR: near-infrared; uPAR: urokinase plasminogen activator receptor

Received: April 27, 2021     Accepted: June 14, 2021     Published: July 06, 2021

Copyright: © 2021 Simón et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

ABSTRACT

The development of tumor-targeted probes that can efficiently reach cancerous tissue is an important focus of preclinical research. Photothermal cancer therapy (PTT) relies on light-absorbing molecules, which are directed towards tumor tissue and irradiated with an external source of light. This light is transformed into heat, causing localized hyperthermia and tumor death. The fluorescent probe indocyanine green (ICG) is already used as an imaging agent both preclinically and in clinical settings, but its use for PTT is yet to be fully exploited due to its short retention time and non-specific tumor targeting. Therefore, increasing ICG tumor uptake is necessary to improve treatment outcome. The urokinase-type plasminogen activator receptor, uPAR, is overexpressed in multiple tumor types. ICG-Glu-Glu-AE105, consisting of the uPAR-targeting peptide AE105 conjugated to ICG, has shown great potential for fluorescence-guided surgery. In this study, ICG-Glu-Glu-AE105 was evaluated as photothermal agent in a subcutaneous mouse model of human glioblastoma. We observed that the photothermal abilities of ICG-Glu-Glu-AE105 triggered high temperatures in the tumor during PTT, leading to tumor death and prolonged survival. This confirms the potential of ICG-Glu-Glu-AE105 as photothermal agent and indicates that it could be used as an add-on to the application of the probe for fluorescence-guided surgery.


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