2. Academic Validation
  3. Shikonin-Cu(II) Supramolecular Polymers Exhibit Antitumor Activity via Necrosis and Cuproptosis

Shikonin-Cu(II) Supramolecular Polymers Exhibit Antitumor Activity via Necrosis and Cuproptosis

  • Adv Healthc Mater. 2025 Feb 24:e2403668. doi: 10.1002/adhm.202403668.
Hongyang Zhang 1 2 3,  Rui-Hong Gong 2 4,  Yu Shan Lin 2,  Tao Wang 2 3,  Dou Luo 2 3,  Jiahua Li 2,  Li-Sha Shen 5,  Wai-Yeung Wong 2 3,  Sibao Chen 2 4 6,  Guo-Qing Chen 1 2
Affiliations

Affiliations

  • 1 College of Pharmacy, Shenzhen Technology University, Shenzhen, 518118, China.
  • 2 The Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen, 518057, China.
  • 3 Department of Applied Biology and Chemical Technology and Research Institute for Smart Energy, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, 999077, China.
  • 4 Department of Food Science and Nutrition, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, 999077, China.
  • 5 Chongqing Academy of Chinese Materia Medica, Chongqing, 400065, China.
  • 6 Research Centre for Chinese Medicine Innovation, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, 999077, China.
PMID: 39989125 DOI: 10.1002/adhm.202403668
Abstract

Supramolecular Polymers driven by the metal-ligand coordination possess reversible bonds, making them promising candidates for integrating the therapeutic functions of metal ions and small-molecule drugs, and subsequently releasing these components within cells after endocytosis. In this study, a kind of supramolecular polymer, SHICU, is developed, composed of Shikonin ligand and Cu(II) ion. Upon reduction by intracellular glutathione (GSH), SHICU dissociates to release Shikonin, Cu(II), and SHICU fragments. The released Shikonin and Cu(II) exhibit a synergistic antitumor effect through the Reactive Oxygen Species (ROS)-dependent necrosis. Meanwhile, the released SHICU that remains structural integrity induces a distinct antitumor mechanism by triggering Cuproptosis in tumor cells. This dual functionality, combining ROS-dependent necrosis and Cuproptosis, highlights the potential of SHICU in advancing antitumor therapies, while the integration of supramolecular Polymers with the emerging cell death mechanism of Cuproptosis facilitates the development of innovative Cancer drugs.

Keywords

Antitumor; Cuproptosis; Necrosis; Shikonin‐Cu(II) complex; Supramolecular polymer.

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