摘要
目的·构建基于纳米工程化的T细胞体系并探究其体外治疗口腔鳞状细胞癌的协同效果,为口腔鳞状细胞癌的治疗提供新策略。方法·制备高亲水性透明质酸(hyaluronic acid,HA)涂层的锆基金属有机框架(Zr-metal-organic framework,Zr-MOF)纳米颗粒(nanoparticle,NP)PCN224-HA NPs,活化其结构上的羧基,使其可以通过酰胺反应与抗CD45抗体偶联。从小鼠脾脏中提取高纯度CD8^(+)T细胞,并利用T细胞表面抗原CD45负载上PCN224-HA,利用生物电镜和共聚焦显微镜观察偶联情况,并检测在超声辐照下自由基的生成。酶标仪记录体外治疗口腔鳞癌Cal27细胞活性变化,探究体外实验的治疗效果。结果·成功合成PCN224-HA NPs,并在生物电镜和共聚焦显微镜上验证其成功偶联上CD8^(+)T细胞的表面,构建纳米工程化T细胞体系(T细胞@PCN224-HA NPs,简称PH T细胞);在超声辐照后监测到自由基产生,进行体外协同治疗后Cal27细胞活性低至31.70%。结论·通过初步实验证明,构建的体系中纳米颗粒能成功负载于T细胞的表面,同时具备纳米颗粒本身的声动力效能和T细胞的免疫杀伤作用的多重功能,可为口腔鳞癌治疗提供新策略,有望用于进一步的体内肿瘤杀伤实验和疾病治疗。
Objective·To construct a nanoengineered T cell system and explore its synergistic efficacy in the in vitro treatment of oral squamous cell carcinoma,and provide a new strategy for this disease.Methods·Zr-MOF nanoparticles with a highly hydrophilic hyaluronic acid(HA)coating(PCN224-HA NPs)were prepared,and their carboxyl groups were activated to enable coupling with anti-CD45 antibodies through an amide reaction.High-purity CD8^(+)T cells were then extracted from the spleens of mice,and the PCN224-HA NPs were loaded onto the T cells via the CD45 antigens on their surface.The coupling was observed using bioelectron microscopy and confocal microscopy,and free radical generation was detected under ultrasound irradiation.The viability of Cal27 cells was recorded by a microplate reader to explore therapeutic effects in vitro.Results·PCN224-HA NPs were successfully synthesized and confirmed to be coupled onto the surface of CD8^(+)T cells,constructing a nanoengineered T cell system(T cells@PCN224-HA NPs).Free radical production was monitored after ultrasound irradiation and the viability of Cal27 cells decreased to 31.70%after in vitro treatment.Conclusions·Preliminary experiments demonstrated that the nanoparticles can be successfully loaded onto the surface of T cells,providing combined sonodynamic therapeutic effects from the nanoparticles and immunocidal effects from the T cells.This offers a novel strategy for the treatment of oral squamous cell carcinoma,with potential for further in vivo anti-tumor experiments and therapeutic applications.
作者
孟靖
谢玉婷
左佳鑫
熊屏
MENG Jing;XIE Yuting;ZUO Jiaxin;XIONG Ping(Department of Ultrasound,Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200011,China;Department of Obstetrics and Gynecology,Fujian Maternal and Child Health Hospital affiliated to Fujian Medical University,Fuzhou 335001,China)
出处
《上海交通大学学报(医学版)》
北大核心
2025年第7期866-873,共8页
Journal of Shanghai Jiao tong University:Medical Science
基金
上海市科学技术委员会基金(23ZR1438000)
上海交通大学医学院附属第九人民医院学科群建设项目(JYJC202132)。
作者简介
通信作者:熊屏,主任医师,博士,电子信箱:xiongpingxp@163.com;第一作者:谢玉婷;第一作者:孟靖。
