摘要
该研究探讨了一种新型仿生纳米药物(PDT@DNPs)的制备方式,并评价了其对卵巢癌细胞ID8的杀伤及对耗竭T细胞的逆转效果。将高表达PD-1的肿瘤细胞膜修饰于DSPE-PEG-MAL与顺铂(DDP)自组装形成的颗粒骨架外,进而构建仿生纳米递送载体PDT@DNPs。采用透射电镜、纳米粒度及电位分析仪等对其形貌特征及粒径、电位等性能进行表征和测定。以ID8细胞为研究对象,通过流式细胞术、激光共聚焦成像、CCK-8(cell counting kit-8)细胞毒性实验、钙黄绿素-AM(Calcein-AM)和碘化丙啶(PI)染色等评价PDT@DNPs的靶向性和杀伤能力;此外,检测T细胞和ID8细胞共孵育体系中乳酸脱氢酶(LDH)的释放水平及细胞因子分泌水平,分析PDT@DNPs对T细胞抗肿瘤免疫的调节能力。上述结果表明,该研究所构建的新型仿生纳米药物PDT@DNPs具有良好的ID8细胞靶向性及杀伤能力,可增强共孵育体系中T细胞的肿瘤细胞杀伤能力。
In this study,a novel biomimetic nanomedicine(PDT@DNPs)was prepared and its killing effect on ID8 cell of ovarian cancer and its reversing effect on exhausted T cells were evaluated.The membrane of tumor cells with high expression of PD-1 was modified on the surface of DSPE-PEG-MAL and DDP(cisplatin)self-assembled particle skeleton to construct a biomimetic nano-delivery vector PDT@DNPs.The morphology,particle size,potential and other properties were characterized and determined by transmission electron microscopy,nanoparticle particle size and potential analyzer.ID8 cells were selected as the study objects.Flow cytometry,laser confocal imaging,CCK-8(cell counting kit-8)cytotoxicity test,Calcein-AM and PI(propyl iodide)staining were used to evaluate the targeting and killing ability of PDT@DNPs.In addition,the release level of LDH(lactate dehydrogenase)and cytokine secretion levels in the co-incubation system of T cells and ID8 cells were detected,and the regulatory ability of PDT@DNPs on the anti-tumor immunity of T cells was analyzed.These results indicated that the novel bionic nanomedicine PDT@DNPs constructed in this study had good ID8 cell targeting and killing ability,and could enhance the tumor cell killing ability of T cells in the co-incubation system.
作者
李玮
高潇涵
孙枝红
刘杰
孙成铭
LI Wei;GAO Xiaohan;SUN Zhihong;LIU Jie;SUN Chengming(Binzhou Medical University,Yantai 264003,China;Yantai Yuhuangding Hospital Affiliated to Qingdao University,Yantai 264000,China;Department of Medicine,Qingdao University,Qingdao 266071,China)
出处
《中国细胞生物学学报》
CAS
CSCD
2023年第11期1651-1660,共10页
Chinese Journal of Cell Biology
基金
山东省自然科学基金(批准号:ZR2022MH100)
烟台市科技计划(批准号:2022MSGY074)资助的课题
关键词
卵巢癌
免疫检查点
细胞膜
化疗
仿生纳米载体
ovarian cancer
immune checkpoints
cell membrane
chemotherapy
bionic nanocarriers
作者简介
通讯作者:孙成铭。Tel:0535-6691999,E-mail:chengmingsun012@163.com
