Development of a multi-functional preclinical device for the treatment of glioblastoma.
Authors: Metwally K, Bastiancich C, Correard F, Novell A, Fernandez S, Guillet B, Larrat B, Mensah S, Estève MA, Da Silva A
Glioblastoma multiforme (GBM) is one of the most common and aggressive malignant primary brain tumors in adults. The treatment of GBM is limited by the blood-brain barrier (BBB), which limits the diffusion of appropriate concentrations of therapeutic agents at the tumor site. Among experimental therapies, photo-thermal therapy (PTT) mediated by nanoparticles is a promising strategy. To propose a preclinical versatile research instrument for the development of new PTT for GBM, a multipurpose integrated preclinical device was developed. The setup is able to perform: i) BBB permeabilization by focused ultrasound sonication (FUS); ii) PTT with continuous wave laser; iii) <i>in situ</i> temperature monitoring with photo-acoustic (PA) measurements. <i>In vivo</i> preliminary subcutaneous and transcranial experiments were conducted on healthy or tumor-bearing mice. Transcranial FUS-induced BBB permeabilization was validated using single photon emission computed tomography (SPECT) imaging. PTT capacities were monitored by PA thermometry, and are illustrated through subcutaneous and transcranial <i>in vivo</i> experiments. The results show the therapeutic possibilities and ergonomy of such integrated device as a tool for the validation of future treatments.
Introduction
Purpose
Drug delivery with BBB opening
Study Objective
To develop and demonstrate a multipurpose integrated preclinical device that combines focused ultrasound BBB permeabilization, continuous-wave laser photo-thermal therapy, and photo-acoustic thermometry for validating nanoparticle-mediated PTT for glioblastoma.
Animal model / Human subject
mouse, C57BL/6, 8–10 weeks, female
Disease model
Glioblastoma multiforme (GBM)
MRI or image guidance method
Single Photon Emission Computed Tomography (SPECT) imaging
Targeted brain region(s)
Striatum
Cargo name and characteristics
Nanoparticles (photothermal nanoparticles used as photo-thermal therapy agents)
Outcomes and Safety
Summary of Outcomes
An integrated platform combined FUS-mediated BBBO for nanoparticle delivery with photoacoustic thermometry-guided PTT, demonstrating enhanced therapeutic control in GBM mice.
Duration of biological effect
not reported
Safety-related matter
The BBBO and PTT procedures were monitored in real-time; no treatment-related adverse effects were observed, and PTT heating was precisely controlled within the target tumor volume.
Brain Region
Ultrasound Parameters
Ultrasound instrument
not reported
FUS Frequency
1.1 MHz
FUS Intensity
not reported
FUS Pressure
0.45 Mpa
FUS Mode
not reported
Pulse duration
not reported
Duration of a single FUS session
60 s
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