Wu Wei, Huang Jiaen, Li Yuling, Chen Jiaxi, Kuang Xiaowei, Ye Manzhen, Chen Rui, An Junli, Huang Zunnan, Sun Jing
The First Dongguan Affiliated Hospital, School of Pharmacy, Guangdong Medical University, Dongguan 523808, P. R. China.
Nancheng Hospital of Dongguan City, Dongguan 523800, P. R. China.
J Med Chem. 2025 Jul 24;68(14):14727-14739. doi: 10.1021/acs.jmedchem.5c00883. Epub 2025 Jul 10.
Cancer immunotherapy has revolutionized oncology by leveraging host immunity to eliminate malignant cells. In this study, five iridium(III) complexes (-) were synthesized and evaluated for their in vitro antitumor activity against various tumor cell lines. Among these, and exhibited the highest cytotoxicity and the most rapid cellular uptake in MDA-MB-231 cells. Colocalization experiments confirmed their accumulation in the endoplasmic reticulum (ER) and their ability to induce pyroptosis. Additionally, both complexes triggered ER stress, leading to increased calreticulin exposure on the cell surface, high-mobility group box 1 secretion, and ATP release, which collectively promoted immunogenic cell death. In vivo, a triple-dose vaccine regimen significantly suppressed tumor growth compared to other treatment groups. These findings highlight the potential of -based novel triple-dose vaccination as a promising cancer immunotherapy strategy.
癌症免疫疗法通过利用宿主免疫力来消除恶性细胞，彻底改变了肿瘤学。在本研究中，合成了五种铱（III）配合物（-），并评估了它们对各种肿瘤细胞系的体外抗肿瘤活性。其中， 和 在MDA-MB-231细胞中表现出最高的细胞毒性和最快的细胞摄取。共定位实验证实了它们在内质网（ER）中的积累以及诱导细胞焦亡的能力。此外，两种配合物均引发内质网应激，导致细胞表面钙网蛋白暴露增加、高迁移率族蛋白B1分泌增加和ATP释放，这些共同促进了免疫原性细胞死亡。在体内，与其他治疗组相比，三剂量疫苗方案显著抑制了肿瘤生长。这些发现突出了基于 -的新型三剂量疫苗接种作为一种有前景的癌症免疫治疗策略的潜力。
