Metalloimmunotherapy with Rhodium and Ruthenium Complexes: Targeting Tumor-Associated Macrophages.
Metalloimmunotherapy with Rhodium and Ruthenium Complexes: Targeting Tumor-Associated Macrophages.
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DOI：
10.1002/chem.202104430
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发表时间：
2022-04-27
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肿瘤相关巨噬细胞（TAM）抑制癌症免疫应答，是免疫治疗的关键靶点。钌和铑络合物对TAM的影响尚未得到很好的表征。为了解决该领域的这一空白，针对三种亚型的巨噬细胞、三阴性乳腺癌和正常乳腺组织细胞筛选了一组22种地铑和钌络合物。实验在有和没有蓝光照射的2D和仿生3D共培养实验中进行。铅被确定为对巨噬细胞亚型、癌细胞或两者具有细胞类型特异性毒性。3D球状体的实验揭示了使肿瘤模型对化疗阿霉素敏感的复合物。钙网蛋白（一种已知的免疫原性细胞死亡（ICD）促进剂）的细胞表面暴露在治疗后增加，沿着M2亚型分类酶的减少。我们的研究结果为靶向TAM的钌和铑基化疗药物的未来发展奠定了坚实的基础。
Tumor associated macrophages (TAMs) suppress the cancer immune response and are a key target for immunotherapy. The effects of ruthenium and rhodium complexes on TAMs have not been well characterized. To address this gap in the field, a panel of 22 dirhodium and ruthenium complexes were screened against three subtypes of macrophages, triple-negative breast cancer and normal breast tissue cells. Experiments were carried out in 2D and biomimetic 3D co-culture experiments with and without irradiation with blue light. Leads were identified with cell-type-specific toxicity toward macrophage subtypes, cancer cells, or both. Experiments with 3D spheroids revealed complexes that sensitized the tumor models to the chemotherapeutic doxorubicin. Cell surface exposure of calreticulin, a known facilitator of immunogenic cell death (ICD), was increased upon treatment, along with a concomitant reduction in the M2-subtype classifier arginase. Our findings lay a strong foundation for the future development of ruthenium- and rhodium-based chemotherapies targeting TAMs.
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影响因子：
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DOI：
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发表时间：
2020-02-01
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哲学分析
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作者：
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影响因子：
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