Hao Zhaokun, Zhou Yuming, Zhang Yuqiang, Wang Danyang, Wei Yiying, Ji Xiaopu, Sun Wan Ru, Wang Pingyu, Li YouJie, Lopez Irene Bautista, Pedraz José Luis, Ramalingam Murugan, Xie Shuyang, Wang Ranran
Institute of Rehabilitation Medicine, School of Rehabilitation Medicine, Binzhou Medical University, Yantai, 264003, People's Republic of China.
Shandong Laboratory of Advanced Materials and Green Manufacturing, Yantai, 264000, People's Republic of China.
Sci Rep. 2025 Apr 16;15(1):13133. doi: 10.1038/s41598-025-97055-7.
Cancer-related pain is prevalent and severely impairs patients' quality of life. However, conventional cancer therapies primarily target tumor cell destruction, often overlooking the management of cancer pain. Thus, there is an immediate necessity to develop therapeutic agents that can both suppress tumor growth and alleviate cancer pain. In this study, we report a celastrol (CEL)-based nanocomposites (PDA-BSA-MnO-CEL) for pain-less cancer immunotherapy. Results from in vitro and in vivo experiments demonstrate the efficacy and mechanism of the nanocomposites in pain-less immunotherapy. MnO and CEL induce immunogenic cell death (ICD), mediating immunotherapy. Additionally, CEL significantly reduces the secretion of the immunosuppressive factor Yes-associated protein (YAP) within the tumor microenvironment, thereby enhancing the efficacy of immunotherapy. The downregulation of YAP leads to reduced expression of vascular endothelial growth factor (VEGF), inhibiting tumor growth and decreasing activation of the pain-associated VEGF receptor 1 (VEGFR1), thus providing an analgesic effect. Moreover, CEL reduces inflammatory pain by lowering levels of inflammatory factors in tumors. The design of this nanocomposites system integrates immunotherapy with cancer pain inhibition, offering a novel approach to patient-centered tumor therapy.
癌症相关疼痛普遍存在，严重损害患者的生活质量。然而，传统的癌症治疗主要针对肿瘤细胞的破坏，常常忽视癌症疼痛的管理。因此，迫切需要开发既能抑制肿瘤生长又能减轻癌症疼痛的治疗药物。在本研究中，我们报道了一种用于无痛癌症免疫治疗的基于雷公藤红素（CEL）的纳米复合材料（PDA-BSA-MnO-CEL）。体外和体内实验结果证明了该纳米复合材料在无痛免疫治疗中的疗效和作用机制。MnO和CEL诱导免疫原性细胞死亡（ICD），介导免疫治疗。此外，CEL显著降低肿瘤微环境中免疫抑制因子Yes相关蛋白（YAP）的分泌，从而提高免疫治疗的疗效。YAP的下调导致血管内皮生长因子（VEGF）表达降低，抑制肿瘤生长并减少疼痛相关血管内皮生长因子受体1（VEGFR1）的激活，从而产生镇痛作用。此外，CEL通过降低肿瘤中炎症因子水平减轻炎性疼痛。这种纳米复合材料系统的设计将免疫治疗与癌症疼痛抑制相结合，为以患者为中心的肿瘤治疗提供了一种新方法。
