The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine, Atlanta, GA, USA.
School of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, GA, USA.
J Nanobiotechnology. 2024 Jun 21;22(1):356. doi: 10.1186/s12951-024-02601-6.
Ultrasound and photoacoustic (US/PA) imaging is a promising tool for in vivo visualization and assessment of drug delivery. However, the acoustic properties of the skull limit the practical application of US/PA imaging in the brain. To address the challenges in targeted drug delivery to the brain and transcranial US/PA imaging, we introduce and evaluate an intracerebral delivery and imaging strategy based on the use of laser-activated perfluorocarbon nanodroplets (PFCnDs).
Two specialized PFCnDs were developed to facilitate blood‒brain barrier (BBB) opening and contrast-enhanced US/PA imaging. In mice, PFCnDs were delivered to brain tissue via PFCnD-induced BBB opening to the right side of the brain. In vivo, transcranial US/PA imaging was performed to evaluate the utility of PFCnDs for contrast-enhanced imaging through the skull. Ex vivo, volumetric US/PA imaging was used to characterize the spatial distribution of PFCnDs that entered brain tissue. Immunohistochemical analysis was performed to confirm the spatial extent of BBB opening and the accuracy of the imaging results.
In vivo, transcranial US/PA imaging revealed localized photoacoustic (PA) contrast associated with delivered PFCnDs. In addition, contrast-enhanced ultrasound (CEUS) imaging confirmed the presence of nanodroplets within the same area. Ex vivo, volumetric US/PA imaging revealed PA contrast localized to the area of the brain where PFCnD-induced BBB opening had been performed. Immunohistochemical analysis revealed that the spatial distribution of immunoglobulin (IgG) extravasation into the brain closely matched the imaging results.
Using our intracerebral delivery and imaging strategy, PFCnDs were successfully delivered to a targeted area of the brain, and they enabled contrast-enhanced US/PA imaging through the skull. Ex vivo imaging, and immunohistochemistry confirmed the accuracy and precision of the approach.
超声和光声（US/PA）成像是一种很有前途的活体可视化和药物输送评估工具。然而，颅骨的声学性质限制了 US/PA 成像在大脑中的实际应用。为了解决脑内靶向药物输送和颅穿透 US/PA 成像的挑战，我们引入并评估了一种基于使用激光激活的全氟碳纳米液滴（PFCnD）的脑内给药和成像策略。
开发了两种专门的 PFCnD，以促进血脑屏障（BBB）开放和对比增强 US/PA 成像。在小鼠中，通过 PFCnD 诱导的 BBB 开放将 PFCnD 递送到大脑右侧的脑组织中。在体内，通过颅穿透进行超声/光声（US/PA）成像，以评估 PFCnD 用于通过颅骨进行对比增强成像的效用。离体，体积超声/光声（US/PA）成像用于表征进入脑组织的 PFCnD 的空间分布。免疫组织化学分析用于确认 BBB 开放的空间范围和成像结果的准确性。
在体内，颅穿透 US/PA 成像显示与递送至的 PFCnD 相关的局部光声（PA）对比。此外，对比增强超声（CEUS）成像证实了纳米液滴存在于同一区域内。离体，体积 US/PA 成像显示 PA 对比定位于 PFCnD 诱导的 BBB 开放区域。免疫组织化学分析显示，免疫球蛋白（IgG）外渗到大脑中的空间分布与成像结果非常吻合。
使用我们的脑内给药和成像策略，成功地将 PFCnD 递送至大脑的靶向区域，并且能够通过颅骨进行对比增强 US/PA 成像。离体成像和免疫组织化学证实了该方法的准确性和精密度。
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