Teixeira Ana Rita C, Antunes Joana, Pinto Catarina I G, Campello Maria Paula Cabral, Santos Pedro, Gomes Célia M, Abrunhosa Antero J, Sampaio Jorge M, Paulo António, Alves Francisco, Mendes Filipa
ICNAS/CIBIT-Institute for Nuclear Sciences Applied to Health/Coimbra Institute for Biomedical Imaging and Translational Research, University of Coimbra, Coimbra, Portugal.
LIP-Laboratório de Instrumentação e Física Experimental de Partículas, Lisboa, Portugal.
Phys Med Biol. 2025 Jun 20;70(12). doi: 10.1088/1361-6560/ade222.
Glioblastoma multiforme (GBM) is the most diagnosed primary brain tumor in adults and remains associated with a poor prognosis due to its aggressive nature. As tumor recurrence is often observed after standard radiation treatment, the use of gold nanoparticles (AuNPs) to improve radiotherapy effectiveness has been proposed as an advanced treatment strategy for this condition. Toward this goal, we investigated the radiosensitizing potential of gastrin releasing peptide receptor (GRPR)-targeted gold nanoparticles (AuNP-BBN) carrying a bombesin peptide (BBN) in glioblastoma cells, when combined withand x-ray radiation and in comparison with their non-targeted counterpart (AuNP-DOTA).Radiation response of U373 and U87 glioblastoma cells was studied upon exposure to Co-60radiation or 160 kVp x-rays and U373 cells were subjected to combined treatment with the AuNPs using the same radiation qualities. The radiobiological effects were assessed via cell viability, clonogenic survival and DNA damage assays, including the determination of the sensitization enhancement ratio (SER). To rationalize the experimental results, Monte Carlo (MC) simulations were performed based on realistic microscopy-based glioblastoma cell models.U373 and U87 cells proved to be more sensitive to x-rays than toradiation. Incubation with AuNP-BBN caused a dose enhancement effect when combined with kilovoltage x-rays but not with Co-60radiation, resulting in reduced U373 cell viability, impaired proliferation and DNA damage. This outcome was not observed in cells treated with the non-targeted AuNP-DOTA, showing that the incorporation of the BBN was crucial for the radiosensitization of GRPR-positive GBM cells. MC simulated radiobiological outcomes were consistent with experimental findings.GRPR-targeted AuNP-BBN are promising nanotools for developing novel treatment strategies for GBM, acting as local and cell-specific radiotherapy enhancers. Their radiosensitizing effects were accurately predicted using an alternative MC simulation method based on realistic microscopy-based cell phantoms.
多形性胶质母细胞瘤（GBM）是成人中最常被诊断出的原发性脑肿瘤，由于其侵袭性，预后仍然很差。由于在标准放射治疗后经常观察到肿瘤复发，因此有人提出使用金纳米颗粒（AuNPs）来提高放射治疗效果，作为针对这种情况的一种先进治疗策略。为了实现这一目标，我们研究了携带蛙皮素肽（BBN）的胃泌素释放肽受体（GRPR）靶向金纳米颗粒（AuNP-BBN）在胶质母细胞瘤细胞中的放射增敏潜力，将其与X射线辐射联合使用，并与非靶向对应物（AuNP-DOTA）进行比较。研究了U373和U87胶质母细胞瘤细胞在暴露于钴-60辐射或160 kVp X射线时的辐射反应，并使用相同的辐射质量对U373细胞进行了与金纳米颗粒的联合治疗。通过细胞活力、克隆形成存活和DNA损伤测定来评估放射生物学效应，包括确定增敏增强率（SER）。为了使实验结果合理化，基于真实的基于显微镜的胶质母细胞瘤细胞模型进行了蒙特卡罗（MC）模拟。U373和U87细胞对X射线比钴-60辐射更敏感。与AuNP-BBN孵育在与千伏X射线联合使用时会产生剂量增强效应，但与钴-60辐射联合使用时则不会，导致U373细胞活力降低、增殖受损和DNA损伤。在用非靶向AuNP-DOTA处理的细胞中未观察到这一结果，表明BBN的掺入对于GRPR阳性GBM细胞的放射增敏至关重要。MC模拟的放射生物学结果与实验结果一致。GRPR靶向的AuNP-BBN是开发GBM新型治疗策略的有前途的纳米工具，可作为局部和细胞特异性放射治疗增强剂。使用基于真实的基于显微镜的细胞模型的替代MC模拟方法准确预测了它们的放射增敏作用。
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