Zhu Anni, Shao Shuai, Hu Jinyuan, Tu Wenzhi, Song Zheming, Liu Yue, Liu Jiansheng, Zhang Qin, Li Jingchao
State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Biological Science and Medical Engineering, Donghua University, Shanghai 201620, China.
Department of Burns and Plastic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China.
Mater Horiz. 2025 Feb 3;12(3):973-986. doi: 10.1039/d4mh01356e.
A variety of therapeutic strategies are available to treat glioblastoma (GBM), but the tumor remains one of the deadliest due to its aggressive invasiveness, restrictive blood-brain barrier (BBB), and exceptional resistance to drugs. In this study, we present a hydrogen sulfide (HS)-generating semiconducting polymer nanoparticle (PFeD@Ang) for amplified radiodynamic-ferroptosis therapy of orthotopic glioblastoma. Our results show that in an acidic tumor microenvironment (TME), HS donors produce large amounts of HS, which inhibits mitochondrial respiration and alleviates cellular hypoxia, thus enhancing the radiodynamic effect during X-ray irradiation; meanwhile, Fe is reduced to Fe by tannic acid in an acidic TME, which promotes an iron-dependent cell death process in tumors. HS facilitates the ferroptosis process by increasing the local HO concentration inhibiting catalase activity. This kind of amplified radiodynamic-ferroptosis therapeutic strategy could remarkably inhibit glioma progression in an orthotopic GBM mouse model. Our study demonstrates the potential of PFeD@Ang for GBM treatment targeted delivery and combinational therapeutic actions of RDT and ferroptosis therapy.
目前有多种治疗策略可用于治疗胶质母细胞瘤（GBM），但由于其侵袭性强、血脑屏障（BBB）限制以及对药物的特殊耐药性，该肿瘤仍然是最致命的肿瘤之一。在本研究中，我们提出了一种用于原位胶质母细胞瘤放大放射动力学-铁死亡治疗的产硫化氢（HS）半导体聚合物纳米颗粒（PFeD@Ang）。我们的结果表明，在酸性肿瘤微环境（TME）中，HS供体产生大量HS，抑制线粒体呼吸并减轻细胞缺氧，从而增强X射线照射期间的放射动力学效应；同时，在酸性TME中，Fe被单宁酸还原为Fe，这促进了肿瘤中铁依赖性细胞死亡过程。HS通过增加局部HO浓度抑制过氧化氢酶活性来促进铁死亡过程。这种放大的放射动力学-铁死亡治疗策略可以显著抑制原位GBM小鼠模型中的胶质瘤进展。我们的研究证明了PFeD@Ang在GBM治疗中的潜力，即RDT和铁死亡治疗的靶向递送和联合治疗作用。
