细胞膜包被碳酸钙纳米粒装载IL-12 mRNA用于超声空化-免疫协同治疗恶性胶质瘤的实验研究

恶性胶质瘤作为最具侵袭性的脑部肿瘤，由于血脑屏障的存在，具有预后差、易复发、死亡率高等特点。激活免疫系统并联合使用核酸药物，因其良好的治疗效果，成为了恶性胶质瘤治疗的新热点。本项目计划设计细胞膜包被的碳酸钙纳米粒，用以递送编码白介素-12的mRNA。其中细胞膜包被可以帮助纳米粒穿越血脑屏障并最终进入恶性胶质瘤细胞，碳酸钙在肿瘤微环境中释放出二氧化碳气体，在超声空化作用下诱导免疫原性坏死，激活免疫应答，最终与翻译出的白介素-12协同增强恶性胶质瘤的免疫治疗效果。本研究的实施，有助于深入研究利用超声诱导免疫原性坏死，并协同核酸类药物进行超声空化-免疫联合治疗的可行性，进而向临床研究转化。

Glioblastoma (GBM) is the most aggressive brain tumor, which has the characteristics of poor prognosis, easy recurrence and high mortality due to the existence of blood brain barrier (BBB). Nowadays, activating the immune system and combined with nucleic acid drugs have attracted much attention due to its positive therapeutic efficiency. In this study, we designed a cancer cell membrane coated calcium carbonate nanoparticle to deliver interleukin-12 mRNA, where the cell membrane coated could help the nanoparticles cross the BBB and eventually enter into GBM cells. Besides, Calcium carbonate nanoparticles release carbon dioxide gas in the tumor microenvironment, which can induce immunogenic necrosis under the ultrasonic cavitation, thereby activate the immune response. Finally combined with the translated interleukin-12 to enhance the immunotherapeutic effect of GBM. Altogether, our study will help explore the feasibility of ultrasonic cavitation-immune combination therapy by using ultrasound induced immunogenic necrosis and nucleic acid drugs. Eventually into clinical research.