Fluorescence lifetime imaging unravels the pathway of glioma cell death upon hypericin-induced photodynamic therapy.

Autor:	Bassler MC; Process Analysis and Technology (PA&T), Reutlingen University Alteburgstr. 150 72762 Reutlingen Germany frank.wackenhut@reutlingen-university.de.; Institute of Physical and Theoretical Chemistry, University of Tübingen Auf der Morgenstelle 18 72076 Tübingen Germany alfred.meixner@uni-tuebingen.de marc.brecht@uni-tuebingen.de., Hiller J; Institute of Physical and Theoretical Chemistry, University of Tübingen Auf der Morgenstelle 18 72076 Tübingen Germany alfred.meixner@uni-tuebingen.de marc.brecht@uni-tuebingen.de., Wackenhut F; Process Analysis and Technology (PA&T), Reutlingen University Alteburgstr. 150 72762 Reutlingen Germany frank.wackenhut@reutlingen-university.de., Zur Oven-Krockhaus S; Institute of Physical and Theoretical Chemistry, University of Tübingen Auf der Morgenstelle 18 72076 Tübingen Germany alfred.meixner@uni-tuebingen.de marc.brecht@uni-tuebingen.de., Frech P; Institute of Physical and Theoretical Chemistry, University of Tübingen Auf der Morgenstelle 18 72076 Tübingen Germany alfred.meixner@uni-tuebingen.de marc.brecht@uni-tuebingen.de., Schmidt F; Institute of Physical and Theoretical Chemistry, University of Tübingen Auf der Morgenstelle 18 72076 Tübingen Germany alfred.meixner@uni-tuebingen.de marc.brecht@uni-tuebingen.de., Kertzscher C; Institute of Physical and Theoretical Chemistry, University of Tübingen Auf der Morgenstelle 18 72076 Tübingen Germany alfred.meixner@uni-tuebingen.de marc.brecht@uni-tuebingen.de., Rammler T; Institute of Physical and Theoretical Chemistry, University of Tübingen Auf der Morgenstelle 18 72076 Tübingen Germany alfred.meixner@uni-tuebingen.de marc.brecht@uni-tuebingen.de., Ritz R; Department of Neurosurgery, Schwarzwald-Baar Clinic 78052 Villingen-Schwenningen Germany., Braun K; Institute of Physical and Theoretical Chemistry, University of Tübingen Auf der Morgenstelle 18 72076 Tübingen Germany alfred.meixner@uni-tuebingen.de marc.brecht@uni-tuebingen.de., Scheele M; Institute of Physical and Theoretical Chemistry, University of Tübingen Auf der Morgenstelle 18 72076 Tübingen Germany alfred.meixner@uni-tuebingen.de marc.brecht@uni-tuebingen.de., Meixner AJ; Institute of Physical and Theoretical Chemistry, University of Tübingen Auf der Morgenstelle 18 72076 Tübingen Germany alfred.meixner@uni-tuebingen.de marc.brecht@uni-tuebingen.de., Brecht M; Process Analysis and Technology (PA&T), Reutlingen University Alteburgstr. 150 72762 Reutlingen Germany frank.wackenhut@reutlingen-university.de.; Institute of Physical and Theoretical Chemistry, University of Tübingen Auf der Morgenstelle 18 72076 Tübingen Germany alfred.meixner@uni-tuebingen.de marc.brecht@uni-tuebingen.de.
Jazyk:	angličtina
Zdroj:	RSC chemical biology [RSC Chem Biol] 2024 Oct 08. Date of Electronic Publication: 2024 Oct 08.
DOI:	10.1039/d4cb00107a
Abstrakt:	Malignant primary brain tumors are a group of highly aggressive and often infiltrating tumors that lack adequate therapeutic treatments to achieve long time survival. Complete tumor removal is one precondition to reach this goal. A promising approach to optimize resection margins and eliminate remaining infiltrative so-called guerilla cells is photodynamic therapy (PDT) using organic photosensitizers that can pass the disrupted blood-brain-barrier and selectively accumulate in tumor tissue. Hypericin fulfills these conditions and additionally offers outstanding photophysical properties, making it an excellent choice as a photosensitizing molecule for PDT. However, the actual hypericin-induced PDT cell death mechanism is still under debate. In this work, hypericin-induced PDT was investigated by employing the three distinct fluorescent probes hypericin, resorufin and propidium iodide (PI) in fluorescence-lifetime imaging microscopy (FLIM). This approach enables visualizing the PDT-induced photodamaging and dying of single, living glioma cells, as an in vitro tumor model for glioblastoma. Hypericin PDT and FLIM image acquisition were simultaneously induced by 405 nm laser irradiation and sequences of FLIM images and fluorescence spectra were recorded to analyze the PDT progression. The reproducibly observed cellular changes provide insight into the mechanism of cell death during PDT and suggest that apoptosis is the initial mechanism followed by necrosis after continued irradiation. These new insights into the mechanism of hypericin PDT of single glioma cells may help to adjust irradiation doses and improve the implementation as a therapy for primary brain tumors. Competing Interests: There are no conflicts to declare. (This journal is © The Royal Society of Chemistry.)
Databáze:	MEDLINE
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