Tao Feng

Drug resistance is a significant challenge for tumor therapy. Activating immunity is an effective method to combat drug‐resistant tumors. Utilizing metallic chemotherapeutic agents to induce nonapoptotic programmed cell death is a practical approach to stimulate immunity. Besides, triggering tumor cell senescence, named senotherapy, is also an effective but often ignored method to induce immune responses. Despite some progress, reports on metallic immunotherapeutic stimuli are sparse and mainly delve into the level of organelle targeting, with vague drug–target mechanisms. Here, we report a Ru(II) complex (Ru2c) inhibits BRD4 with high affinity at a nanomolar constant. After encapsulation into biotin‐DNA cage, Ru2c@biotin‐DNA cage was demonstrated to kill drug‐resistant cancer cells through a synergistic apoptosis‐ferroptosis‐senescence pathway, exhibiting 51‐fold anticancer activity compared to the commercial inhibitor JQ‐1. Ru2c effectively erased drug‐resistant tumors and activated innate and acquired immunity in vivo. To the best of our knowledge, Ru2c is the first metal‐based BRD4 inhibitor to achieve synergistic seno‐immunotherapy and chemo‐immunotherapy.

Five osmium(II) polypyridyl complexes of the general formula [Os(4,7‐diphenyl‐1,10‐phenanthroline)₂L]²⁺ were synthesized as photosensitizers for photodynamic therapy by varying the nature of the ligand L. Thanks to the pronounced π‐extended structure of the ligands and the heavy atom effect provided by the osmium center, these complexes exhibit a high absorption in the near‐infrared (NIR) region (up to 740 nm), unlike related ruthenium complexes. This led to a promising phototoxicity in vitro against cancer cells cultured as 2D cell layers but also in multicellular tumor spheroids upon irradiation at 740 nm. The complex [Os(4,7‐diphenyl‐1,10‐phenanthroline)₂(2,2′‐bipyridine)]²⁺ was found to be the most efficient against various cancer cell lines, with high phototoxicity indexes. Experiments on CT26 tumor‐bearing BALB/c mice also indicate that the Os^II complexes could significantly reduce tumor growth following 740 nm laser irradiation. The high phototoxicity in the biological window of this structurally simple complex makes it a promising photosensitizer for cancer treatment.

Five osmium(II) polypyridyl complexes of the general formula [Os(4,7‐diphenyl‐1,10‐phenanthroline)₂L]²⁺ were synthesized as photosensitizers for photodynamic therapy by varying the nature of the ligand L. Thanks to the pronounced π‐extended structure of the ligands and the heavy atom effect provided by the osmium center, these complexes exhibit a high absorption in the near‐infrared (NIR) region (up to 740 nm), unlike related ruthenium complexes. This led to a promising phototoxicity in vitro against cancer cells cultured as 2D cell layers but also in multicellular tumor spheroids upon irradiation at 740 nm. The complex [Os(4,7‐diphenyl‐1,10‐phenanthroline)₂(2,2′‐bipyridine)]²⁺ was found to be the most efficient against various cancer cell lines, with high phototoxicity indexes. Experiments on CT26 tumor‐bearing BALB/c mice also indicate that the Os^II complexes could significantly reduce tumor growth following 740 nm laser irradiation. The high phototoxicity in the biological window of this structurally simple complex makes it a promising photosensitizer for cancer treatment.