黑色素协同NO/ROS/RNS联合引发的肿瘤细胞凋亡对免疫激活的依赖性研究

近几年，肿瘤NO治疗、光动力治疗和光热治疗因其良好治疗效果和低毒性得到广泛关注。但以上治疗引发的肿瘤消融，是否同化疗一样依赖于诱发的肿瘤及机体免疫激活，还没有明确结论。课题组已证实，当采用靶向黑色素纳米颗粒对抗体清除小鼠进行肿瘤治疗时，小鼠肿瘤生长速度明显低于正常小鼠，这提示光热治疗引发的肿瘤凋亡对机体免疫功能具有强烈依赖性。另外，课题组通过特定氨基酸接枝制备得到的黑色素（MNP）-Ce6纳米颗粒同时具备光热及近红外光催化能力，且与负载NO供体的OBN微囊共存时可释放细胞杀伤力更强的RNS。这一工作为研究肿瘤NO、光动力和光热联合治疗提供了良好基础。我们拟应用基因表达谱、基因敲除及抗体中和等手段，验证黑色素协同NO/ROS/RNS实现的肿瘤凋亡是否依赖于治疗过程中引发的肿瘤免疫激活。该研究对明确光热、光动力辅助产生的免疫激活在肿瘤凋亡中的地位具有重要意义。

In recent years, tumor NO therapy, photodynamic therapy and photothermal therapy have received widespread attention because of their good therapeutic effect and low toxicity.However, whether the tumor ablation induced by the above treatments (which is like chemotherapy) is dependent on the tumor immune activation has not been clearly concluded. The melanin (MNP) -Ce6 nanoparticles prepared by our research group have been proved to have both photothermal and ROS producing abilities, and the nanoparticles can release RNS which has more cytotoxicity when coexisting with the OBN microcapsules loaded with NO donor. This work provides a good basis for the study of multimodal combined therapy of NO, photodynamic and photothermal tumors. In addition, our research group has confirmed that, when antibody-cleared mice were treated with targeted melanin nanoparticles, the tumor growth rate of mice was significantly lower than that of normal mice, suggesting that photothermal treatment-induced tumor apoptosis has a strong dependence on the tumor's and the body's immune function. In this study, we intend to use gene expression profiles, metabolomics analysis and antibody neutralization to verify whether the MNP/NO/ROS/RNS-induced tumor apoptosis depends on the tumor immune activation initiated during treatment. This study is of great significance for clarifying the role of immune activation initiated during photothermal/photodynamic/NO combined therapy in tumor apoptosis.