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.
Highlights
The development of new and more efficient ways to induce localized tumor death without damaging healthy tissue is still a need in cancer treatment and management
Photothermal cancer therapy (PTT) holds great potential; this therapy relies on photoabsorbing molecules, which are directed towards tumor tissue, and are able to transform the near-infrared (NIR) light they are irradiated with into heat, causing highly localized tumor death through hyperthermia [1, 2]
We investigated the potential of ICGGlu-Glu-AE105 for image-guided photothermal cancer therapy in a subcutaneous xenograft mouse model of human glioblastoma
Summary
The development of new and more efficient ways to induce localized tumor death without damaging healthy tissue is still a need in cancer treatment and management. Other molecules with photothermal abilities are being investigated This includes indocyanine green (ICG), a fluorophore that is FDA approved for determining cardiac output, liver blood flow and hepatic function as well as ophthalmic angiography [4, 5]. It is currently being tested in clinical trials as a probe for fluorescence-guided surgery [6]. The properties of ICG have been studied preclinically, but a short circulation and retention time in tumor tissue are considerable limitations to the use of ICG as a photothermal agent [7,8,9]. As a higher degree of tumor retention of ICG would improve treatment outcome, some studies have focused on achieving a more specific tumor accumulation of ICG by using an ICG-loaded nanocarrier or by linking the fluorophore to a molecule targeting tumor components [10,11,12]
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