University Chemistry ›› 2025, Vol. 40 ›› Issue (7): 200-212.doi: 10.12461/PKU.DXHX202410024

• Survey of Chemistry • Previous Articles     Next Articles

Ruthenium(II) Complexes as Photoactivated Chemo-Prodrugs for Hypoxic Tumor Therapy

Fa Wang, Yu Chen, Hui Chao   

  1. MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-Sen University, Guangzhou 510006, China
  • Received:2024-10-08 Accepted:2024-12-09 Published:2025-07-01
  • Contact: Yu Chen, Hui Chao E-mail:chenyu63@mail.sysu.edu.cn;ceschh@mail.sysu.edu.cn

Abstract: The toxic side effects resulting from the low selectivity of chemotherapeutic drugs are a significant challenge in clinical treatment. Photoactivated therapy can achieve precise regulation of drug activity at the tumor site with the help of spatial and temporal modulation of light, which minimizes the toxic side effects. Hypoxia is a characteristic of solid tumors. Therefore, oxygen-independent photoactivated chemotherapy (PACT) matches the requirements of hypoxic tumor treatment. Due to their rich photophysical and photochemical properties, Ru(II) complexes are potential candidates for constructing PACT prodrugs. Upon irradiation, Ru(II)-based PACT prodrugs generate Ru(II)-solvent species and free ligands, which subsequently bind to biomolecules to inhibit their biological functions, and the latter usually also possess DNA-damaging or protein-inhibiting abilities, further enhancing the antitumor activity. The rational design strategy of Ru(II)-based PACT prodrugs is still unclear. Herein, we briefly introduce the research progress of Ru(II)-based PACT prodrugs to overcome hypoxic tumors from the perspective of ligand coordination number based on the photoactivation mechanism, preliminarily explore their molecular design strategies, summarize the challenges faced in this field and look forward to their future applications. We hope this review will provide a reference for the design of new efficient and low-toxic Ru(II)-based PACT prodrugs.

Key words: Ruthenium(II) complexes, Photoactivated chemotherapy, Antitumor, Hypoxia