Abstract：
Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor and known for its challenging prognosis. Sonodynamic therapy (SDT) is an innovative therapeutic approach that shows promise in tumor elimination by activating sonosensitizers with low-intensity ultrasound. In this study, a novel sonosensitizer is synthesized using Cu-doped carbon dots (Cu-CDs) for the sonodynamic treatment of GBM. Doping with copper transforms the carbon dots into a p-n type semiconductor having a bandgap of 1.58 eV, a prolonged lifespan of 10.7 µs, and an improved electron- and hole-separation efficiency. The sonodynamic effect is efficiency enhanced. Western blot analysis reveals that the Cu-CDs induces a biological response leading to cell death, termed as cuproptosis. Specifically, Cu-CDs upregulate dihydrosulfanyl transacetylase expression, thereby establishing a synergistic therapeutic effect against tumor cell death when combined with SDT. Furthermore, Cu-CDs exhibit excellent permeability through the blood-brain barrier and potent anti-tumor activity. Importantly, the Cu-CDs effectively impede the growth of glioblastoma tumors and prolong the survival of mice bearing these tumors. This study provides support for the application of carbon-based nanomaterials as sonosensitizers in tumor therapy.
摘要：
多形性胶质母细胞瘤（GBM）是最常见的原发性恶性脑肿瘤，以其具有挑战性的预后而闻名。声动力疗法（SDT）是一种创新的治疗方法，通过低强度超声激活声敏剂来消除肿瘤。在这项研究中,使用Cu掺杂的碳点（Cu-CD）合成了一种新型的超声敏化剂，用于GBM的声动力处理。用铜掺杂将碳点转变为带隙为1.58eV的p-n型半导体，延长了10.7µs的寿命，以及改进的电子和空穴分离效率。声动力效应是效率提高。蛋白质印迹分析显示，Cu-CD诱导导致细胞死亡的生物反应，称为角化。具体来说,Cu-CD上调二氢硫酰乙酰基转移酶表达，从而当与SDT组合时建立对抗肿瘤细胞死亡的协同治疗效果。此外，Cu-CD表现出优异的通过血脑屏障的渗透性和有效的抗肿瘤活性。重要的是,Cu-CD有效地阻止胶质母细胞瘤肿瘤的生长并延长携带这些肿瘤的小鼠的存活。本研究为碳基纳米材料作为超声增敏剂在肿瘤治疗中的应用提供了支持。
