Metal‐Doping Strategy for Carbon‐Based Sonosensitizer in Sonodynamic Therapy of Glioblastoma

• Published in: Advanced science Vol. 11; no. 34; pp. e2404230 - n/a
• Main Authors: Cheng, Mingming, Liu, Yan, You, Qiannan, Lei, Zhubing, Ji, Jiajian, Zhang, Fan, Dong, Wen‐Fei, Li, Li
• Format: Journal Article
• Language: English
• Published: Germany John Wiley & Sons, Inc 01.09.2024; John Wiley and Sons Inc; Wiley
• Subjects: Animals; Apoptosis; Brain cancer; Brain Neoplasms - therapy; Carbon; Carbon - chemistry; carbon dots; Cell death; Cell Line, Tumor; Conductivity; Copper; Copper - chemistry; Copper - pharmacology; Cytotoxicity; Disease Models, Animal; Electrodes; Electrons; Energy; Glioblastoma - therapy; glioblastoma multiforme; Glioma; Humans; Mice; Nanoparticles; Quantum dots; Semiconductors; sonodynamic therapy; Spectrum analysis; Transmission electron microscopy; Ultrasonic Therapy - methods; United States > US; carbon dots; glioblastoma multiforme; copper; sonodynamic therapy
• ISSN: 2198-3844; 2198-3844
• DOI: 10.1002/advs.202404230

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. A novel carbon‐based sonosensitizer doped with copper (Cu‐CDs) is developed for the sonodynamic therapy of glioblastoma. The Cu‐CDs enhance the efficiency of reactive oxygen species (ROS) production by promoting electron–hole separation. Additionally, Cu‐CDs exhibit excellent penetration efficiency across the blood‐brain barrier and achieve a synergistic tumor‐killing effect through sonodynamic therapy and cuproptosis, thereby significantly inhibiting glioblastoma growth.