TY - JOUR

T1 - The use of a uPAR-targeted probe for photothermal cancer therapy prolongs survival in a xenograft mouse model of glioblastoma

AU - Simón, Marina

AU - Jørgensen, Jesper Tranekjær

AU - Juhl, Karina

AU - Kjaer, Andreas

N1 - Publisher Copyright: Copyright: © 2021 Simón et al.

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

KW - Cancer

KW - Hyperthermia

KW - Indocyanine green (ICG)

KW - Photothermal therapy (PTT)

KW - Urokinase plasminogen activator receptor (uPAR)

UR - http://www.scopus.com/inward/record.url?scp=85109508793&partnerID=8YFLogxK

U2 - 10.18632/oncotarget.28013

DO - 10.18632/oncotarget.28013

M3 - Journal article

C2 - 34262647

AN - SCOPUS:85109508793

VL - 12

SP - 1366

EP - 1376

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 14

ER -