工程化纳米囊泡结合化疗用于增强肿瘤免疫治疗

Engineered nanovesicles combined with chemotherapy for enhancing tumor immunotherapy

目的:结合免疫治疗与化疗,以改善肿瘤的治疗效果,为安全有效的肿瘤免疫治疗策略的发展提供更多见解。方法:使用工程化纳米囊泡,囊泡膜上表达PD-1受体,可以靶向肿瘤细胞表面的PD-L1,通过破坏PD-1/PD-L1免疫抑制通路增强抗肿瘤反应。同时,囊泡包裹的化疗药物阿霉素可以进入肿瘤细胞核,抑制DNA与RNA的合成,诱导肿瘤细胞死亡。结果:实验证实,制备的PD1-阿霉素材料具备良好的稳定性、安全性,能准确靶向肿瘤部位,阿霉素在细胞核部位起作用,能有效地进行肿瘤杀伤。结论:本研究首次将PD-1免疫检查点抑制与化疗药物阿霉素相结合,利用PD-1囊泡安全性高、长循环的特点作为包裹化疗药物阿霉素的载体,这种方法可以进行肿瘤细胞的有效靶向与治疗,实现肿瘤的有效清除。

Objective To combine immunotherapy with chemotherapy for improving the therapeutic effect,and providing more insights for the development of safe and effective tumor immunotherapy strategies.Methods The engineered nanovesicles were used in the study.The PD-1 receptors expressed on the vesicle membrane targeted PD-L1 on the surface of tumor cells and enhanced the anti-tumor response by disrupting the PD-1/PD-L1 immunosuppressive pathway.Meanwhile,vesicles-encapsulated chemotherapy drug doxorubicin(DOX)entered the tumor nucleus,inhibited the synthesis of DNA and RNA,and induced tumor cell death.Results Experiments confirmed that the prepared PD1-DOX had good stability and high safety,and could accurately target the tumor site.DOX worked at the nucleus to effectively kill tumors.Conclusion This is the first time to combine PD-1 immune checkpoint inhibition with DOX.Because of characteristics of high safety and long circulation,the PD-1 vesicles are taken as the carrier for encapsulating DOX.The prepared material can effectively target and treat tumor cells and achieve effective tumor clearance.