The biomedical application of corannulene π-bowls is historically limited by low solubility and bioavailability despite the potential in their unique electronic properties for new functional materials. Herein, the unexpected role and molecular mechanism of Corranulene π-bowls are uncovered in biomedical applications as an effective anticancer agent for Warburg effect mediated selective tumor targeting. The corannulene triazolyl monosaccharides Cor-sugars exhibit highly potent cytotoxicity against human cancer cells and effectively inhibit xenograft growth of hyperglycolytic tumors. Particularly, the galactose-conjugated Cor-gal exhibits superior in vivo anticancer efficacy in A549 tumor models with outstanding safety profile compared to doxorubicin. Moreover, the combined treatment of Cor-gal with immune checkpoint inhibitor results in an effective synergy in treating H460 human lung carcinoma. An uptake mechanism study reveals that Cor-sugars exploit tumor-specific glucose transporter glucose transporter 1 (GLUT1) for targeted cell delivery and intra-tumoral accumulation through the cancer-specific Warburg effect. Their significant anticancer activity is attributed to multiphasic DNA-binding and cell cycle alteration effects. This study uncovers new molecular properties of corannulene buckybowl and enabling their potential new applications in biomedical engineering.

中文翻译：

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Corannulene Buckybowl 糖缀合物通过靶向癌症特异性 Warburg 效应在选择性肿瘤湮灭中的未揭示分子功能

corannulene π -bowls的生物医学应用在历史上受到低溶解度和生物利用度的限制，尽管它们具有用于新功能材料的独特电子特性的潜力。在此，Corranulene π的意想不到的作用和分子机制- 碗在生物医学应用中被发现是一种有效的抗癌剂，用于 Warburg 效应介导的选择性肿瘤靶向。Corannulene 三唑基单糖 Cor-sugars 对人类癌细胞表现出高效的细胞毒性，并有效抑制高糖酵解肿瘤的异种移植物生长。特别是，与多柔比星相比，半乳糖缀合的 Cor-gal 在 A549 肿瘤模型中表现出优异的体内抗癌功效，具有出色的安全性。此外，Cor-gal 与免疫检查点抑制剂的联合治疗在治疗 H460 人肺癌方面产生了有效的协同作用。一项摄取机制研究表明，Cor-sugars 利用肿瘤特异性葡萄糖转运蛋白葡萄糖转运蛋白 1 (GLUT1) 通过癌症特异性 Warburg 效应进行靶向细胞递送和肿瘤内积累。它们显着的抗癌活性归因于多相 DNA 结合和细胞周期改变效应。这项研究揭示了corannulene buckybowl的新分子特性，并使其在生物医学工程中具有潜在的新应用。