上海口腔医学

上海口腔医学 ›› 2026, Vol. 35 ›› Issue (1): 7-12.doi: 10.19439/j.sjos.2026.01.002

• 论著 • 上一篇    下一篇

T1-T2双模态钴锰氧化物纳米MRI造影剂在口腔鳞癌成像中的应用评价

许弘弢1, 程瀚1, 李方杰2, 郑重阳1, 黄小娟1, 张志愿1   

  1. 1.上海交通大学医学附属第九人民医院 口腔颌面头颈肿瘤科,上海交通大学口腔医学院, 国家口腔医学中心,口腔疾病国家临床医学研究中心,上海市口腔医学重点实验室, 上海市口腔医学研究所,上海 200011;
    2.湖州大学第一附属医院 口腔颌面外科,浙江 湖州 313000
  • 收稿日期:2025-01-23 修回日期:2025-03-24 出版日期:2026-03-12 发布日期:2026-03-12
  • 通讯作者: 张志愿, E-mail:zhzhy0502@126.com
  • 作者简介:许弘弢（1998-）,男,在读硕士研究生,E-mail: xuhongtao@sjtu.edu.cn
  • 基金资助:
    国家自然科学基金(82002853); 上海市口腔疾病临床医学研究中心科研项目(19MC1910600); 上海市临床重点专科(shslczdzk01601); 上海市重中之重研究中心科研项目(2022ZZ01017); 中国医学科学院医学与健康科技创新工程项目(2019-I2M-5-037)

Application of T1-T2 dual-mode cobalt manganese oxide nanoparticle MRI contrast agent in the diagnosis of oral squamous cell carcinoma

Xu Hongtao1, Cheng Han1, Li Fangjie2, Zheng Chongyang1, Huang Xiaojuan1, Zhang Zhiyuan1   

  1. 1. Department of Oromaxillofacial Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology; Shanghai Research Institute of Stomatology. Shanghai 200011;
    2. Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Huzhou University. Huzhou 313000, Zhejiang Province, China
  • Received:2025-01-23 Revised:2025-03-24 Online:2026-03-12 Published:2026-03-12

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摘要： 目的 开发一种高效低毒的T1-T2双模态MRI纳米造影剂（cobalt manganese oxide @hyaluronic acid, CMO@HA）,为口腔鳞癌的诊断提供一种安全有效的新策略。方法 通过多步合成法制备CMO@HA,采用透射电镜（TEM）、X射线衍射（XRD）等方法表征其形貌及成分;利用MR成像系统采集不同浓度CMO@HA悬浮液的T1-T2加权图像及弛豫时间,通过线性回归分析其纵向、横向弛豫率。构建异种移植小鼠模型,评估CMO@HA的体内肿瘤成像性能。通过CCK-8细胞活性检测、活/死细胞染色以及主要脏器的HE染色等方法,评估其生物相容性。结果 成功合成HA修饰的钴锰基氧化物CMO@HA,粒径约为12 nm,Zeta电位为-16.6 mV。MR性能试验中,CMO@HA溶液表现出浓度依赖的T1-T2双模态加权成像特性,纵向和横向弛豫率分别为1.005 (mmol/L)-1s-1和11.84 (mmol/L)-1s-1。异种移植小鼠模型中,瘤内注射CMO@HA后,肿瘤部位的T1加权、T2加权信号分别增强(46.98±14.51)%和(26.04±6.9)%。生物相容性测试结果表明,在100 μg/mL浓度CMO@HA共培养后,细胞活性仍保持98%,活/死细胞染色结果与对照组无显著差异。在7天观察期内,CMO@HA处理小鼠的体重与对照组基本一致,主要脏器未见病理损伤,无明显肝、肾功能损伤。结论 CMO@HA是一种具备T1-T2双模态MRI成像增强能力且生物相容性良好的纳米造影剂,可显著提高肿瘤组织与正常组织的成像对比度,为口腔鳞癌的早期诊断提供了可行的影像学解决方案。

关键词: 口腔鳞癌, 肿瘤成像, 钴锰氧化物纳米颗粒, MRI造影剂

Abstract: PURPOSE: To develop an efficient and low-toxicity T1-T2 dual-mode magnetic resonance (MR) nano-contrast agent (cobalt manganese oxide @hyaluronic acid, CMO@HA) as a safe and effective strategy for the diagnosis of oral squamous cell carcinoma (OSCC). METHODS: CMO@HA was synthesized via a multi-step process and characterized for its morphology and composition using transmission electron microscopy(TEM) and X-ray diffraction (XRD). MR imaging of CMO@HA suspensions at various concentrations was performed to acquire T1- and T2-weighted images and relaxation times. The longitudinal and transverse relaxivities were calculated using linear regression analysis. A xenograft mouse model was established to evaluate the in vivo tumor imaging performance of CMO@HA. Biocompatibility was assessed through CCK-8 cell viability assays, live-dead cell staining and HE staining of major organs. RESULTS: CMO@HA was successfully synthesized with an average particle size of approximately 12 nm and a zeta potential of -16.6 mV. In MRI, CMO@HA solutions exhibited concentration-dependent T1-T2 dual-enhanced imaging characteristics, with longitudinal and transverse relaxivities of 1.005 (mmol/L)-1s-1 and 11.84 (mmol/L)-1s-1, respectively. In the xenograft mouse model, intratumoral injection of CMO@HA resulted in an enhancement of T1-weighted and T2-weighted signals at the tumor site by (46.98±14.51)% and (26.04±6.9)%, respectively. Biocompatibility assessments revealed that after co-incubation with 100 μg/mL CMO@HA, the cell viability remained at 98%, live-dead staining results showed no significant differences compared to the control group. During a 7-day observation period, CMO@HA-treated mice exhibited stable body weights comparable to the control group, and no pathological damage or liver and kidney dysfunction was observed in major organs. CONCLUSIONS: CMO@HA is a nano-contrast agent with excellent T1-T2 dual-mode MR imaging enhancement capabilities and favorable biocompatibility. It significantly improves the imaging contrast between tumor and normal tissues, providing a viable imaging solution for early diagnosis of OSCC.

Key words: Oral squamous cell carcinoma, Tumor imaging, Cobalt manganese oxide nanoparticles, MRI contrast agent

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