上海口腔医学

上海口腔医学 ›› 2026, Vol. 35 ›› Issue (2): 121-128.doi: 10.19439/j.sjos.2026.02.002

• 论著 • 上一篇    下一篇

具核梭杆菌搭载BiS/CeO2复合纳米棒对口腔鳞癌的光热、化学动力及免疫治疗的协同效应评价

邹子川1,2, 孟箭1,2, 李昂1,2, 杨昊楠2, 王守鹏2, 杨沛鸣2, 陈寅瑜2   

  1. 1.徐州医科大学徐州临床学院 江苏 徐州 221000;
    2.徐州市中心医院 口腔科,江苏 徐州 221000
  • 收稿日期:2025-01-17 修回日期:2025-05-06 出版日期:2026-04-25 发布日期:2026-04-27
  • 通讯作者: 孟箭,E-mail：mrocket@126.com
  • 作者简介:邹子川（1999—）,男,在读硕士研究生,住院医师,E-mail：dentalzzc@126.com
  • 基金资助:
    国家口腔疾病临床医学研究中心开放课题（NCRCO-202101）; 徐州市优秀人才基金项目（XYFY202207,XYFY202334）

Evaluation of the synergistic effects of F.nucleatum loaded with BiS/CeO2 composite nanorods on photothermal, chemodynamic and immunotherapy in oral squamous cell carcinoma

Zou Zichuan1,2, Meng Jian1,2, Li Ang1,2, Yang Haonan2, Wang Shoupeng2, Yang Peiming2, Chen Yinyu2   

  1. 1. The Xuzhou Clinical College of Xuzhou Medical University. Xuzhou 221000;
    2. Department of Stomatology, Xuzhou Central Hospital. Xuzhou 221000, Jiangsu Province, China
  • Received:2025-01-17 Revised:2025-05-06 Online:2026-04-25 Published:2026-04-27

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摘要： 目的:制备搭载硫化铋（bismuth sulfide,BiS）/氧化铈（ceric dioxide,CeO2）复合纳米棒的活性具核梭杆菌（F.nucleatum,Fn）生物递送系统（BiS/CeO2@Fn）,对其进行性质表征,初步探讨其对口腔鳞癌（oral squamous cell carcinoma,OSCC）的抗肿瘤功效。方法:采用水热法合成BiS/CeO2复合纳米棒,通过静电吸附作用制备BiS/CeO2@Fn。采用透射电镜（transmission electron microscope,TEM）、激光纳米粒度/电位仪分别对BiS/CeO2@Fn微观形态、平均粒径及 Zeta电位进行表征,采用近红外热成像仪记录808 nm激光照射后BiS/CeO2@Fn的光热性能。通过监测体系中氧气（O2）和羟基自由基（hydroxyl radicals,·OH）的产生,评价BiS/CeO2@Fn的过氧化氢酶（catalase,CAT）活性和过氧化物酶（peroxidase,POD）活性。使用氧气荧光探针,评估BiS/CeO2@Fn促进CAL27细胞胞内O2生成的作用。使用DCFH-DA 探针,评估BiS/CeO2@Fn在细胞内产生活性氧（reactive oxygen species,ROS）的作用。通过活/死细胞双染色、细胞增殖检测,评价BiS/CeO2@Fn对 CAL27细胞的协同杀伤效应;通过监测胞内ATP含量及钙网蛋白（calreticulin,CRT）和高迁移率族蛋白B1（high mobility group protein B1,HMGB1）免疫荧光染色,确定免疫原性细胞死亡（immunogenic cell death,ICD）效应。结果:BiS/CeO2纳米棒粒径为（303.21±5.83） nm,Zeta 电位为（4.70±1.30） mV。TEM下观察,搭载具核梭杆菌后,BiS/CeO2@Fn长杆菌外缘可见明显纳米颗粒附着。BiS/CeO2@Fn具有良好的光热效应、显著的 CAT 和POD酶活性;BiS/CeO2@Fn可缓解肿瘤组织乏氧环境,促进ROS生成,降低肿瘤细胞活力,促进ICD标志性信号分子的表达。结论:BiS/CeO2@Fn活菌生物递送系统可发挥光热消融、化学动力学和免疫治疗的协同作用,对肿瘤细胞产生显著杀伤作用。

关键词: 口腔鳞癌, 具核梭杆菌, 光热治疗, 化学动力治疗, 免疫治疗

Abstract: PURPOSE: This study aims to develop an active F.nucleatum (Fn) bio-delivery system (BiS/CeO2@Fn) loaded with composite nanorods and to characterize its properties. The antitumor efficacy of BiS/CeO2@Fn against oral squamous cell carcinoma (OSCC) was preliminarily evaluated. METHODS: Bismuth sulfide/cerium oxide (BiS/CeO2) composite nanorods were synthesized using a hydrothermal method, and BiS/CeO2@Fn was prepared via electrostatic adsorption. The micromorphology, average particle size, and Zeta potential were characterized using transmission electron microscopy (TEM) and a laser nanoparticle size/potentiometer. The photothermal performance of BiS/CeO2@Fn under 808 nm laser irradiation was recorded using a near-infrared thermal imaging camera. The catalase (CAT) and peroxidase (POD) activities of BiS/CeO2@Fn were evaluated by monitoring the production of O2 and hydroxyl radicals (·OH). Intracellular reactive oxygen species (ROS) and O2 generation was assessed using a DCFH-DA probe and an oxygen fluorescent probe, respectively. The synergistic cytotoxicity effect of BiS/CeO2@Fn on CAL27 cells was investigated through live/dead cell staining and cell proliferation assays. Immunogenic cell death (ICD) effects were examined by monitoring intracellular ATP levels and immunofluorescence staining for calreticulin (CRT) and high mobility group protein B1 (HMGB1). Results: The synthesized BiS/CeO2 nanorods exhibited a mean diameter of approximately 303.21 nm and a Zeta potential of (4.70±1.30) mV. TEM image revealed distinct adherence of nanoparticles around the bacteria following incubation with Fn, indicating the successful fabrication of BiS/CeO2@Fn. This composite demonstrated excellent photothermal conversion efficiency and significant CAT and POD catalytic activities. Furthermore, BiS/CeO2@Fn not only effectively alleviated tumor hypoxia, but also prompted ROS generation, suppressed tumor cell viability, and upregulated the expression of ICD hallmark molecules. CONCLUSIONS: The BiS/CeO2@Fn live bacterial bio-delivery system demonstrates a synergistic cytotoxicity against CAL27 tumor cells through photothermal ablation, chemical dynamics therapy and immunotherapy. This multifunctional delivery system demonstrates significant therapeutic potential for treatment of OSCC.

Key words: Oral squamous cell carcinoma, F.nucleatum, Photothermal therapy, Chemodynamic therapy, Immunotherapy

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