Department of Radiology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China.
Center for Molecular Imaging and Nuclear Medicine, State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X), Suzhou Medical College of Soochow University, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Suzhou, 215123, China.
Biomater Sci. 2023 Sep 12;11(18):6252-6266. doi: 10.1039/d3bm00897e.
The complete treatment of high grade invasive glioblastoma (GBM) remains to be a great challenge, and it is of great importance to develop innovative therapeutic approaches. Herein, we found that GBM derived from U87 MG cells is a glutamine-addiction tumor, and jointly using glutamine-starvation therapy and photo-enhanced chemodynamic therapy (CDT) can significantly boost its therapy. We rationally fabricated tumor cell membrane coated CuSe nanoparticles (CS NPs) and an inhibitor of glutamine metabolism (Purpurin) for combined therapy, because glutamine rather than glucose plays a crucial role in the proliferation and growth of GBM cells, and serves as a precursor for the synthesis of glutathione (GSH). The resultant CS-P@CM NPs can be specifically delivered to the tumor site to inhibit glutamine metabolism in tumor cells, suppress tumor intracellular GSH, and increase HO content, which benefit the CDT catalyzed by CS NPs. The cascade reaction can be further enhanced by irradiation with the second near-infrared (NIR-II) light at the maximum concentration of HO, which can be monitored by photoacoustic imaging. The NIR-II light irradiation can generate a large amount of reactive oxygen species (ROS) within a short time to kill tumor cells and enhance the CDT efficacy. This is the first work on the treatment of orthotopic malignant GBM through combined glutamine metabolism therapy and photo-enhanced CDT, and provides insights into the treatment of other solid tumors by modulating the metabolism of tumor cells.
高级别浸润性神经胶质瘤（GBM）的完全治疗仍然是一个巨大的挑战，因此开发创新的治疗方法非常重要。在这里，我们发现源自 U87 MG 细胞的 GBM 是一种谷氨酰胺成瘾肿瘤，联合使用谷氨酰胺饥饿疗法和光增强化学动力学疗法（CDT）可以显著增强其治疗效果。我们合理地制备了细胞膜包覆的 CuSe 纳米粒子（CS NPs）和谷氨酰胺代谢抑制剂（Purpurin）用于联合治疗，因为谷氨酰胺而不是葡萄糖在 GBM 细胞的增殖和生长中起着至关重要的作用，并且作为谷胱甘肽（GSH）合成的前体。所得的 CS-P@CM NPs 可以特异性递送至肿瘤部位以抑制肿瘤细胞中的谷氨酰胺代谢，抑制肿瘤细胞内的 GSH，并增加 HO 含量，这有利于 CS NPs 催化的 CDT。在 HO 的最大浓度下用第二近红外（NIR-II）光照射可以进一步增强级联反应，可通过光声成象进行监测。NIR-II 光照射可以在短时间内产生大量的活性氧（ROS）来杀死肿瘤细胞并增强 CDT 疗效。这是通过联合谷氨酰胺代谢疗法和光增强 CDT 治疗原位恶性 GBM 的首次尝试，并为通过调节肿瘤细胞代谢来治疗其他实体瘤提供了思路。
