Department of Neurology, Second Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China.
Department of General Practice, Second Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China.
Nanomedicine. 2022 Jul;43:102554. doi: 10.1016/j.nano.2022.102554. Epub 2022 Mar 28.
Glioblastoma (GBM) is the most fatal and common type of primary malignant tumors in central nervous system. Chemotherapy drugs are difficult to reach the encephalic region effectively due to blood-brain barrier (BBB), but functional nanoparticle drug carriers can help to solve the problem. Herein, we developed a controllable drug carrier called temozolomide magnetic temperature-sensitive liposomes (TMZ/Fe-TSL) to investigate its feasibility and molecular mechanisms on GBM. Our research found TMZ/Fe-TSL exposed to alternating magnetic field (AMF) could induce significantly GBM cell death and promote the production of ROS. It also showed that the expression of NLRP3, CASP1 and N-GSDMD was upregulated compared to the control group, while the expression of CASP3 showed a reverse change. The results indicated that TMZ/Fe-TSL exposed to the AMF was capable of inducing GBM cells death. And the way and mechanisms of cell death may involve in ROS and pyroptosis, but not apoptosis.
胶质母细胞瘤（GBM）是中枢神经系统中最致命和最常见的原发性恶性肿瘤。由于血脑屏障（BBB）的存在，化疗药物难以有效地到达脑部区域，但功能性纳米药物载体可以帮助解决这个问题。在此，我们开发了一种名为替莫唑胺磁热敏脂质体（TMZ/Fe-TSL）的可控药物载体，以研究其在 GBM 中的可行性和分子机制。我们的研究发现，暴露于交变磁场（AMF）的 TMZ/Fe-TSL 可以显著诱导 GBM 细胞死亡，并促进 ROS 的产生。结果还表明，与对照组相比，NLRP3、CASP1 和 N-GSDMD 的表达上调，而 CASP3 的表达则呈相反变化。结果表明，暴露于 AMF 的 TMZ/Fe-TSL 能够诱导 GBM 细胞死亡。细胞死亡的方式和机制可能涉及 ROS 和细胞焦亡，但不涉及细胞凋亡。
