An Unrevealed Molecular Function of Corannulene Buckybowl Glycoconjugates in Selective Tumor Annihilation by Targeting the Cancer‐Specific Warburg Effect. Issue 10 (7th March 2022)

• Record Type: Journal Article
• Authors: Liu, Shengnan; Sun, Ziru; Liang, Min; Song, Weijie; Zhang, Ru; Shi, Yunli; Cui, Yujun; Gao, Qingzhi
• Is Part Of: Advanced science. Volume 9:Issue 10(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-03-07
• Subjects: anticancer -- corannulene -- DNA binding -- glucose transporter -- Warburg effect; Science -- Periodicals; 505
• DOI: 10.1002/advs.202105315
• Languages: English
• ISSNs: 2198-3844

Abstract

Abstract: 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. Abstract : Sugar‐conjugated corannulene π ‐bowls possess a new molecular function in DNA interactive anticancer therapy. Corannulene‐sugar conjugates can be transported through glucose transporter 1 (GLUT1) for cancer cell uptake and effectively annihilate xenograft tumors by leveraging the Warburg effect. The anticancer activity relies on a unique multiphasic DNA binding mechanism of the curved corannulene molecule and selectively induces cell cycle arrest in tumor cells.