Development and optimisation of in vitro sonodynamic therapy for glioblastoma.
Development and optimisation of in vitro sonodynamic therapy for glioblastoma.
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胶质母细胞瘤体外声动力学治疗的发展和优化。
DOI：
10.1038/s41598-023-47562-2
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发表时间：
2023-11-18
影响因子：
4.6
通讯作者：
中科院分区：
文献类型：
--
作者：
声动力疗法(SDT)是目前治疗胶质母细胞瘤的关键手段。SDT是一种非侵入性方法，利用聚焦超声波激活光敏剂，如5-ALA，以阻止肿瘤生长。不幸的是，SDT治疗功能的分子机制仍然是个谜。这主要是由于缺乏复杂的优化仪器，能够在体外调节SDT向胶质瘤细胞的输送。因此，关于SDT对胶质瘤干细胞的影响的信息很少，而胶质瘤干细胞是胶质瘤发生和复发的关键驱动因素。为了解决这一问题，本研究开发并验证了一种自动化的体外SDT系统，以允许在不同的曝光条件和设置配置下应用和绘制聚焦超声场。这项研究优化了超声频率、强度、平板基材、热效应和活细胞的整合。事实上，在5-ALA存在的情况下，聚焦超声诱导原发患者来源的胶质瘤细胞的凋亡细胞死亡，同时细胞内活性氧物种上调。有趣的是，原发胶质瘤干细胞神经球在SDT暴露后也表现出显著的3D生长减少。综上所述，该研究报告了一种基于组织培养的疾病模型的SDT应用的体外系统，以潜在地对当前护理标准的新方法进行基准测试。
Sonodynamic therapy (SDT) is currently on critical path for glioblastoma therapeutics. SDT is a non-invasive approach utilising focused ultrasound to activate photosensitisers like 5-ALA to impede tumour growth. Unfortunately, the molecular mechanisms underlying the therapeutic functions of SDT remain enigmatic. This is primarily due to the lack of intricately optimised instrumentation capable of modulating SDT delivery to glioma cells in vitro. Consequently, very little information is available on the effects of SDT on glioma stem cells which are key drivers of gliomagenesis and recurrence. To address this, the current study has developed and validated an automated in vitro SDT system to allow the application and mapping of focused ultrasound fields under varied exposure conditions and setup configurations. The study optimizes ultrasound frequency, intensity, plate base material, thermal effect, and the integration of live cells. Indeed, in the presence of 5-ALA, focused ultrasound induces apoptotic cell death in primary patient-derived glioma cells with concurrent upregulation of intracellular reactive oxygen species. Intriguingly, primary glioma stem neurospheres also exhibit remarkably reduced 3D growth upon SDT exposure. Taken together, the study reports an in vitro system for SDT applications on tissue culture-based disease models to potentially benchmark the novel approach to the current standard-of-care.
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影响因子：
82.9
作者：
Klughammer J;Kiesel B;Roetzer T;Fortelny N;Nemc A;Nenning KH;Furtner J;Sheffield NC;Datlinger P;Peter N;Nowosielski M;Augustin M;Mischkulnig M;Ströbel T;Alpar D;Ergüner B;Senekowitsch M;Moser P;Freyschlag CF;Kerschbaumer J;Thomé C;Grams AE;Stockhammer G;Kitzwoegerer M;Oberndorfer S;Marhold F;Weis S;Trenkler J;Buchroithner J;Pichler J;Haybaeck J;Krassnig S;Mahdy Ali K;von Campe G;Payer F;Sherif C;Preiser J;Hauser T;Winkler PA;Kleindienst W;Würtz F;Brandner-Kokalj T;Stultschnig M;Schweiger S;Dieckmann K;Preusser M;Langs G;Baumann B;Knosp E;Widhalm G;Marosi C;Hainfellner JA;Woehrer A;Bock C
通讯作者：
Bock C
影响因子：
3.3
作者：
Kessel D
通讯作者：
Kessel D
影响因子：
4
作者：
通讯作者：
--
影响因子：
64.5
作者：
Venkataramani，Varun;Yang，Yvonne;Winkler，Frank
通讯作者：
Winkler，Frank
影响因子：
5.6
作者：
Eljamel S
通讯作者：
Eljamel S