光声影像导航免疫原性纳米粒改善腹腔免疫微环境抑制卵巢癌复发与转移的研究

卵巢癌复发及转移是导致其死亡率居高不下的重要原因，而残留病灶及腹腔微环境免疫抑制导致的免疫逃逸是影响卵巢癌复发及转移的重要因素。故探索既可特异识别及靶向清除残留病灶又可阻止肿瘤免疫逃逸的方法对提高卵巢癌患者的生存率十分重要。项目组前期研究发现腹腔内巨噬细胞可作为转运体输送造影剂到达肿瘤区域并增强超声介导的靶向杀伤。但由于卵巢癌腹腔内巨噬细胞多处于非活化状态且造影剂粒径大，其转运效率仍然较低。本课题基于脂多糖对巨噬细胞的活化作用、奥沙利铂的免疫原性细胞死亡诱导作用及液态氟碳相变特性，合成脂多糖包裹的携氧载奥沙利铂/吲哚箐绿纳米造影剂（LOI_NPs），探讨激光触发LOI_NPs对ID8细胞的肿瘤抗原暴露作用；建立免疫活性小鼠腹腔转移瘤模型，通过光声成像导航治疗，探讨该纳米粒对卵巢癌复发及转移的抑制效应及腹腔免疫微环境的调节作用，为卵巢癌患者提供一种新型的光声影像导航的光化学-免疫治疗模式。

Ovaran cancer is the most deathly gynecology cancer for tumor recurrence and metastasis after primary tumor-debulking operation. Lines of pre-clinical and clinical evidences suggest that the residual lesions and tumor immunosuppression microenvironment induced tumor immune escape is a key contributing factor for tumor recurrence and metastasis. Therefore, it is very important to explore a method that can not only recognize and remove small residual lesions but also improve the abdominal immune microenvironment. In the previous study, it was found that intraperitoneal macrophages could be used as transporters to transport oxygen-carrying microbubble contrast agents to the hypoxic areas of tumors and enhance the ultrasound mediated treatment. However, due to the large size of the contrast agent and the non-activation of the peritoneal macrophages of ovarian cancer, the transshipment efficiency of contrast agent is still low. Based on the activation of lipopolysaccharide to macrophages, immune-cell death induction of oxaliplatin and the phase transition characteristics of liquid fluorocarbon, we synthesized the lipopolysaccharide coated oxygen and ICG-OXA loaded nanoparticle(LOI_NPs) for laser mediated delivery of oxygen and drugs with photoacoustic imaging guidance. We hypothesize that this multifunctional nanoparticle not only enhancing the therapeutic efficiency of residual lesions but also improving intraperitoneal immune status to control the recurrence and metastasis of ovarian cancer. This hypothesis will tested experimentally in ovarian cancer ID8 cells in vitro and abdominal metastatic ovarian cancer model with normal immunity in vivo. This study may provide a new way provide a photoacoustic image guided photochemical-immunotherapy for ovarian cancer .