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Accumulation and penetration behavior of hypericin in glioma tumor spheroids studied by fluorescence microscopy and confocal fluorescence lifetime imaging microscopy

  • Glioblastoma WHO IV belongs to a group of brain tumors that are still incurable. A promising treatment approach applies photodynamic therapy (PDT) with hypericin as a photosensitizer. To generate a comprehensive understanding of the photosensitizer-tumor interactions, the first part of our study is focused on investigating the distribution and penetration behavior of hypericin in glioma cell spheroids by fluorescence microscopy. In the second part, fluorescence lifetime imaging microscopy (FLIM) was used to correlate fluorescence lifetime (FLT) changes of hypericin to environmental effects inside the spheroids. In this context, 3D tumor spheroids are an excellent model system since they consider 3D cell–cell interactions and the extracellular matrix is similar to tumors in vivo. Our analytical approach considers hypericin as probe molecule for FLIM and as photosensitizer for PDT at the same time, making it possible to directly draw conclusions of the state and location of the drug in a biological system. The knowledge of both state and location of hypericin makes a fundamental understanding of the impact of hypericin PDT in brain tumors possible. Following different incubation conditions, the hypericin distribution in peripheral and central cryosections of the spheroids were analyzed. Both fluorescence microscopy and FLIM revealed a hypericin gradient towards the spheroid core for short incubation periods or small concentrations. On the other hand, a homogeneous hypericin distribution is observed for long incubation times and high concentrations. Especially, the observed FLT change is crucial for the PDT efficiency, since the triplet yield, and hence the O2 activation, is directly proportional to the FLT. Based on the FLT increase inside spheroids, an incubation time  30 min is required to achieve most suitable conditions for an effective PDT.

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Metadaten
Author of HS ReutlingenBassler, Miriam; Wackenhut, Frank; Secic, Ivona; Brecht, Marc
URN:urn:nbn:de:bsz:rt2-opus4-39936
DOI:https://doi.org/10.1007/s00216-022-04107-2
ISSN:1618-2642
eISSN:1618-2650
Erschienen in:Analytical & bioanalytical chemistry
Publisher:Springer
Place of publication:Heidelberg
Translator:Marc Brecht
Document Type:Journal article
Language:English
Publication year:2022
Tag:fluorescence lifetime; fluorescence microscopy; hypericin; photodynamic therapy; tumor spheroid
Volume:414
Page Number:12
First Page:4849
Last Page:4860
PPN:Im Katalog der Hochschule Reutlingen ansehen
DDC classes:540 Chemie
Open access?:Ja
Licence (German):License Logo  Creative Commons - CC BY - Namensnennung 4.0 International