Dataset Information

Development and optimisation of in vitro sonodynamic therapy for glioblastoma.

ABSTRACT: 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.

SUBMITTER: Keenlyside A

PROVIDER: S-EPMC10657375 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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Development and optimisation of in vitro sonodynamic therapy for glioblastoma.

Keenlyside Andrew A Marples Theodore T Gao Zifan Z Hu Hong H Nicely Lynden Guy LG Nogales Joaquina J Li Han H Landgraf Lisa L Solth Anna A Melzer Andreas A Hossain-Ibrahim Kismet K Huang Zhihong Z Huang Zhihong Z Banerjee Sourav S Joseph James J

Scientific reports 20231118 1

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 ...[more]

PMID: 37980454

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Project description:Sonodynamic therapy (SDT) has aroused great interest for its potential in the treatment of glioblastoma (GBM). SDT relies on tumor-selective accumulation of a sonosensitizer that is activated by ultrasound irradiation (UI) to generate cytotoxic actions. The efficacy of GBM-SDT depends on sufficient sonosensitizer buildup in the tumor, which is, however, seriously hampered by the anatomical and biochemical barriers of the GBM. To overcome this difficulty, we herein propose a delivery strategy of 'platelets with ultrasound-triggered release property', which takes advantage of 1) the platelets' ability to carry cargo and release cargo upon activation, and 2) the ROS-generating property of SDT. To provide proof of concept for the strategy, we first stably loaded platelets with IOPD-Ce6, a nano-formed sonosensitizer consisting of iron oxide nanoparticles coated with polyglycerol and doxorubicin and loaded with chlorine e6. UI of the IOPD-Ce6-loaded platelets (IOPD-Ce6@Plt) elicited ROS generation in the IOPD-Ce6@Plt, which were immediately activated to release IOPD-Ce6 into GBM cells in co-culture which, when subjected to a second time of UI, exhibited pronounced ROS production, DNA injury, viability loss, and cell death in the GBM cells. In the in vivo experiments, mice bearing intracranial GBM grafts exhibited substantial tumor distribution of IOPD-Ce6 following intravenous injection of IOPD-Ce6@Plt and subsequent UI at the tumor site. The GBM grafts then exhibited pronounced cell injury and death after another round of UI of the tumors. Finally, the growth of intra-cranial GBM grafts was significantly slowed when an SDT protocol consisting of an intravenous IOPD-Ce6@Plt injection followed by multiple times of tumor UI had been applied twice to the mice. Our results are strong evidence for the idea that platelets are sound and amenable carriers to deliver sonosensitizers in the GBM in an ultrasound-triggered manner and thus to produce highly targeted and effective SDT of GBM.

Dataset Information

Development and optimisation of in vitro sonodynamic therapy for glioblastoma.

Publications

Development and optimisation of in vitro sonodynamic therapy for glioblastoma.

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