Department of Biomedical Engineering, National Yang Ming Chiao Tung University, Taipei, Taiwan; Cell Therapy Center, China Medical University Hospital, Taichung, Taiwan.
Department of Biomedical Engineering, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Acta Biomater. 2021 Apr 15;125:300-311. doi: 10.1016/j.actbio.2021.02.019. Epub 2021 Feb 17.
Although boron neuron capture therapy (BNCT) has enabled the delivery of stronger radiation dose to glioblastoma multiforme (GBM) cells for precision radiotherapy (RT), patients in need are almost unable to access the treatment due to insufficient operating devices. Therefore, we developed targeted sensitization-enhanced radiotherapy (TSER), a strategy that could achieve precision cell-targeted RT using common linear accelerators. TSER, which involves the combination of GoldenDisk (GD; a spherical radioenhancer), 5-aminolevulinic acid (5-ALA), low-intensity ultrasound (US), and low-dose RT, exhibited synergized radiosensitization effects. Both 5-ALA and hyaluronic-acid-immobilized GD can selectively accumulate in GBM to induce chemical and biological enhancement of radiosensitization, resulting in DNA damage, escalation of reactive oxygen species levels, and cell cycle redistribution, in turn sensitizing GBM cells to radiation under US. TSER showed an enhanced therapeutic effect and survival in the treatment of an orthotropic GBM model with only 20% of the radiation dose compared to that of a 10-Gy RT. The strategy with the potential to inhibit GBM progress and rescue the organ at risk using low-dose RT, thereby improving the quality of life of GBM patients, shedding light on achieving cell-targeted RT using universally available linear accelerators. STATEMENT OF SIGNIFICANCE: We invented GoldenDisk (GD), a radioenhancer with hyaluronic-acid (HAc)-coated gold nanoparticle (AuNP)-core/silica shell nanoparticle, to make radiotherapy (RT) safer and smarter. The surface modification of HAc and silica allows GD to target CD44-overexpressed glioblastoma multiforme (GBM) cells and stay structurally stable in cytoplasm throughout the course of RT. By combining GD with low-energy ultrasound and an FDA-approved imaging agent, 5-aminolevulinic acid (5-ALA), GBM cells were sensitized to RT leaving healthy tissues in the vicinity unaffected. The ionized radiation can further be transferred to photoelectronic products with higher cytotoxicity by GD upon collision, achieving higher therapeutic efficacy. With the newly-developed strategy, we are able to achieve low-dose precision RT with the use of only 20% radiation dose.
虽然硼神经元捕获疗法（BNCT）能够为多形性胶质母细胞瘤（GBM）细胞提供更强的辐射剂量，实现精准放疗（RT），但由于设备不足，几乎所有需要的患者都无法接受这种治疗。因此，我们开发了靶向增敏增强放疗（TSER），这是一种利用普通直线加速器实现精确细胞靶向 RT 的策略。TSER 结合了金球（GD；一种球形辐射增强剂）、5-氨基酮戊酸（5-ALA）、低强度超声（US）和低剂量 RT，表现出协同的放射增敏作用。5-ALA 和透明质酸固定的 GD 都可以选择性地积聚在 GBM 中，诱导放射增敏的化学和生物学增强，导致 DNA 损伤、活性氧水平的增加和细胞周期的重新分布，从而使 GBM 细胞在 US 下对辐射敏感。TSER 在治疗原位 GBM 模型时显示出增强的治疗效果和存活率，与 10GyRT 相比，只需 20%的辐射剂量。该策略有可能使用低剂量 RT 抑制 GBM 进展并挽救危险器官，从而提高 GBM 患者的生活质量，为使用普遍可用的直线加速器实现细胞靶向 RT 提供了思路。
