Roberto Miriam, Ali Meedie, Que Ivo, Stefania Rachele, de Bruijn Henriette S, Robinson Dominic J, Blasi Francesco, D'Andrea Luca D, Terreno Enzo, Mezzanotte Laura
Department of Molecular Biotechnology and Health Sciences, Molecular & Preclinical Imaging Centers, University of Torino, Torino, Italy.
Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.
Photochem Photobiol. 2025 Sep-Oct;101(5):1241-1250. doi: 10.1111/php.14097. Epub 2025 Apr 2.
Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor, with a median overall survival of 14.6 months. GBM is incurable because of its invasive growth. These local invasive cells, most significantly glioblastoma stem cells (GSCs), when left behind, resist standard treatment, and cause almost all recurrences. However, the treatment of these infiltrative margins remains a significant challenge, as there are currently no options to reach these margins safely. Photodynamic therapy (PDT) shows promise as localized treatment option using light-activated compounds that target tumor cells and that generate reactive oxygen species (ROS) to destroy them. Far red light, combined with silicon phthalocyanines, could penetrate deeper making it more effective for reaching cancer cells in the tumor margin without compromise of healthy brain. In this study, we used patient-derived GBM spheroids in vitro as a preclinical model to evaluate a new dual-cRGDfK-silicon phthalocyanine conjugate targeting integrin αvβ3, a protein expressed by GBM cells and vasculature. Targeted PDT was efficient in killing GSC spheroids, showing that the combination of far-red light with more precise targeting can reach the type of cells found in the invasive margin, using silicon phthalocyanine as the photosensitizer.
多形性胶质母细胞瘤（GBM）是最具侵袭性的原发性脑肿瘤，中位总生存期为14.6个月。由于其浸润性生长，GBM无法治愈。这些局部浸润性细胞，尤其是胶质母细胞瘤干细胞（GSCs），若残留下来，会抵抗标准治疗，并导致几乎所有的复发。然而，治疗这些浸润边缘仍然是一项重大挑战，因为目前没有安全到达这些边缘的方法。光动力疗法（PDT）作为一种局部治疗选择显示出前景，它使用光激活化合物靶向肿瘤细胞并产生活性氧（ROS）来破坏它们。远红光与硅酞菁结合，可以穿透得更深，使其在不损害健康脑组织的情况下，更有效地到达肿瘤边缘的癌细胞。在本研究中，我们在体外使用患者来源的GBM球体作为临床前模型，来评估一种新的靶向整合素αvβ3的双cRGDfK-硅酞菁共轭物，整合素αvβ3是一种由GBM细胞和脉管系统表达的蛋白质。靶向光动力疗法在杀死GSC球体方面很有效，表明以硅酞菁作为光敏剂，远红光与更精确的靶向相结合可以到达在浸润边缘发现的细胞类型。
