Your browser doesn't support javascript.
loading
Accumulation and penetration behavior of hypericin in glioma tumor spheroids studied by fluorescence microscopy and confocal fluorescence lifetime imaging microscopy.
Bassler, Miriam C; Rammler, Tim; Wackenhut, Frank; Zur Oven-Krockhaus, Sven; Secic, Ivona; Ritz, Rainer; Meixner, Alfred J; Brecht, Marc.
Afiliação
  • Bassler MC; Process Analysis and Technology (PA&T), Reutlingen University, Alteburgstr. 150, 72762, Reutlingen, Germany.
  • Rammler T; Institute of Physical and Theoretical Chemistry, University of Tübingen, Auf der Morgenstelle 18, 72076, Tübingen, Germany.
  • Wackenhut F; Institute of Physical and Theoretical Chemistry, University of Tübingen, Auf der Morgenstelle 18, 72076, Tübingen, Germany.
  • Zur Oven-Krockhaus S; Process Analysis and Technology (PA&T), Reutlingen University, Alteburgstr. 150, 72762, Reutlingen, Germany. frank.wackenhut@reutlingen-university.de.
  • Secic I; Institute of Physical and Theoretical Chemistry, University of Tübingen, Auf der Morgenstelle 18, 72076, Tübingen, Germany.
  • Ritz R; Process Analysis and Technology (PA&T), Reutlingen University, Alteburgstr. 150, 72762, Reutlingen, Germany.
  • Meixner AJ; Department of Neurosurgery, Schwarzwald-Baar Clinic, Klinikstr. 11, 78052, Villingen-Schwenningen, Germany.
  • Brecht M; Institute of Physical and Theoretical Chemistry, University of Tübingen, Auf der Morgenstelle 18, 72076, Tübingen, Germany.
Anal Bioanal Chem ; 414(17): 4849-4860, 2022 Jul.
Article em En | MEDLINE | ID: mdl-35538227
ABSTRACT
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.
Assuntos
Palavras-chave

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Perileno / Neoplasias Encefálicas / Glioma Limite: Humans Idioma: En Revista: Anal Bioanal Chem Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Alemanha

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Perileno / Neoplasias Encefálicas / Glioma Limite: Humans Idioma: En Revista: Anal Bioanal Chem Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Alemanha