荧光寿命成像揭示了金丝桃素诱导的光动力疗法导致胶质瘤细胞死亡的途径。

IF 4.2 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY RSC Chemical Biology Pub Date : 2024-10-08 DOI:10.1039/d4cb00107a
Miriam C Bassler, Jonas Hiller, Frank Wackenhut, Sven Zur Oven-Krockhaus, Philipp Frech, Felix Schmidt, Christoph Kertzscher, Tim Rammler, Rainer Ritz, Kai Braun, Marcus Scheele, Alfred J Meixner, Marc Brecht
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引用次数: 0

摘要

恶性原发性脑肿瘤是一类侵袭性极强的肿瘤,通常具有浸润性,缺乏足够的治疗手段来实现长期生存。彻底切除肿瘤是实现这一目标的前提条件之一。光动力疗法(PDT)是优化切除边缘和消除残留浸润性所谓游击细胞的一种很有前景的方法,它使用的有机光敏剂可以通过被破坏的血脑屏障,并选择性地在肿瘤组织中积聚。金丝桃素符合这些条件,而且具有出色的光物理特性,是光动力疗法光敏剂分子的绝佳选择。然而,金丝桃素诱导光透析细胞死亡的实际机制仍存在争议。本研究采用荧光-寿命成像显微镜(FLIM),利用三种不同的荧光探针--金丝桃素、雷索卢芬和碘化丙啶(PI),研究了金丝桃素诱导的光致透射疗法。作为胶质母细胞瘤的体外肿瘤模型,这种方法可以观察到由光致沉着诱导的单个活体胶质瘤细胞的光损伤和死亡。通过 405 nm 激光照射,同时诱导金丝桃素 PDT 和 FLIM 图像采集,并记录 FLIM 图像和荧光光谱序列,以分析 PDT 的进展。可重复观察到的细胞变化深入揭示了 PDT 过程中的细胞死亡机制,并表明细胞凋亡是最初的机制,随后是持续照射后的坏死。这些对单个胶质瘤细胞的金丝桃素光导透射机制的新认识可能有助于调整照射剂量,改善原发性脑肿瘤的治疗效果。
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Fluorescence lifetime imaging unravels the pathway of glioma cell death upon hypericin-induced photodynamic therapy.

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.

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CiteScore
6.10
自引率
0.00%
发文量
128
审稿时长
10 weeks
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