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Photodynamic Therapy Using a Heavy-Atom-Free G‑Quadruplex-Targeted Photosensitizer to Efficiently Regress
Eva Rodriguez-Marquez1, Hanna Nord1, Darío Puchán Sánchez2
1Department of Medical and Translational Biology, Umeå University, 90187 Umeå, Sweden.
Abstract:
Rhabdomyosarcoma is a highly aggressive soft tissue cancer that predominantly affects children and adolescents. Current treatment outcomes are poor, highlighting the urgent need for potent therapeutic alternatives. Preclinical research on photodynamic therapy (PDT) continues to gain attention as a promising and minimally invasive treatment strategy. Recently, PDT using the heavy-atom-free photosensitizer dibenzothioxanthene imide (DBI), which targets cancer-associated G-quadruplex (G4) DNA, has demonstrated high efficacy at nanomolar concentrations. In here, transgenic zebrafish with rhabdomyosarcoma tumors were utilized to evaluate the therapeutic potential of DBI treatment. We demonstrate that photoactivated DBI efficiently induce localized tumor necrosis, resulting in significant rhabdomyosarcoma regression compared to untreated controls. In fact, in comparison to the healthy cells surrounding the tumor, a high level of G4s was detected, as visualized by a G4-specific antibody. Notably, muscle and nerve cells within the treated tumor area were particularly affected, further underscoring its potency. These findings position DBI as a promising candidate for PDT in the treatment of rhabdomyosarcoma, offering selective G4-targeting capabilities and delivering robust therapeutic outcomes in in vivo models.
Insights
Dibenzothioxanthene imide (DBI) photodynamic therapy shows promise for treating aggressive rhabdomyosarcoma. Photoactivated DBI effectively targets G-quadruplex DNA, causing tumor regression in zebrafish models.
Area of Science:
- Oncology
- Biochemistry
- Biomedical Engineering
Background:
- Rhabdomyosarcoma is an aggressive pediatric soft tissue cancer with poor treatment outcomes.
- Photodynamic therapy (PDT) is a minimally invasive treatment strategy gaining traction.
- Heavy-atom-free photosensitizers offer novel therapeutic avenues.
Purpose of the Study:
- To evaluate the therapeutic efficacy of dibenzothioxanthene imide (DBI) in a preclinical rhabdomyosarcoma model.
- To assess the G-quadruplex (G4) targeting capability of DBI in vivo.
- To determine the potential of DBI-mediated PDT for rhabdomyosarcoma treatment.
Main Methods:
- Utilized transgenic zebrafish with rhabdomyosarcoma tumors.
- Administered photoactivated dibenzothioxanthene imide (DBI).
- Visualized G-quadruplex DNA using a G4-specific antibody.
Main Results:
- Photoactivated DBI induced localized tumor necrosis and significant rhabdomyosarcoma regression.
- High levels of G-quadruplex DNA were detected in tumor cells compared to healthy surrounding cells.
- Muscle and nerve cells within the tumor area were notably affected by the treatment.
Conclusions:
- Dibenzothioxanthene imide (DBI) demonstrates potent efficacy in treating rhabdomyosarcoma via photodynamic therapy.
- DBI selectively targets G-quadruplex DNA, leading to robust therapeutic outcomes in vivo.
- DBI represents a promising candidate for developing novel rhabdomyosarcoma treatments.
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