上海交通大学学报（医学版）

上海交通大学学报（医学版） >

2025 , Vol. 45 >Issue 7: 866 - 873

DOI: https://doi.org/10.3969/j.issn.1674-8115.2025.07.008

论著 · 基础研究

纳米工程化T细胞体系的构建及其对口腔鳞状细胞癌的体外治疗研究

  • 孟靖 ,
  • 谢玉婷 ,
  • 左佳鑫 ,
  • 熊屏
展开
  • 1.上海交通大学医学院附属第九人民医院超声医学科，上海 200011
    2.福建医科大学附属福建省妇幼保健院妇产科，福州 335001
第一联系人：孟靖、 谢玉婷为共同第一作者(co-first authors)。
熊　屏，主任医师，博士；电子信箱：xiongpingxp@163.com。

收稿日期: 2025-01-08

  录用日期: 2025-04-11

  网络出版日期: 2025-07-28

基金资助

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)

收起

Nanoengineered T cell system for the in vitro treatment of oral squamous cell carcinoma

  • MENG Jing ,
  • XIE Yuting ,
  • ZUO Jiaxin ,
  • XIONG Ping
Expand
  • 1.Department of Ultrasound, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
    2.Department of Obstetrics and Gynecology, Fujian Maternal and Child Health Hospital affiliated to Fujian Medical University, Fuzhou 335001, China
XIONG Ping, E-mail: xiongpingxp@163.com.

Received date: 2025-01-08

  Accepted date: 2025-04-11

  Online published: 2025-07-28

Supported by

Project of Shanghai Science and Technology Commission(23ZR1438000);Project for Disciplinary Group Construction of Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine(JYJC202132)

Fold

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。

关键词： 口腔鳞状细胞癌; 声动力治疗; 免疫治疗; 纳米工程化T细胞体系; PCN224-HA纳米颗粒; CD8? T细胞; 协同治疗

本文引用格式

孟靖 , 谢玉婷 , 左佳鑫 , 熊屏 . 纳米工程化T细胞体系的构建及其对口腔鳞状细胞癌的体外治疗研究[J]. 上海交通大学学报（医学版）, 2025 , 45(7) : 866 -873 . DOI: 10.3969/j.issn.1674-8115.2025.07.008

Abstract

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.

Key words： oral squamous cell carcinoma; sonodynamic therapy; immunotherapy; nanoengineered T cells; PCN224-HA nanoparticle; CD8+ T cell; synergistic therapy

参考文献

[1] JOHNSON D E, BURTNESS B, LEEMANS C R, et al. Head and neck squamous cell carcinoma[J]. Nat Rev Dis Primers, 2020, 6(1): 92.
[2] CHOW L Q M. Head and neck cancer[J]. N Engl J Med, 2020, 382(1): 60-72.
[3] TABERNA M, MENA M, PAVóN M A, et al. Human papillomavirus-related oropharyngeal cancer[J]. Ann Oncol, 2017, 28(10): 2386-2398.
[4] GRABOYES E M, KOMPELLI A R, NESKEY D M, et al. Association of treatment delays with survival for patients with head and neck cancer: a systematic review[J]. JAMA Otolaryngol Head Neck Surg, 2019, 145(2): 166-177.
[5] SOLOMON B, YOUNG R J, RISCHIN D. Head and neck squamous cell carcinoma: genomics and emerging biomarkers for immunomodulatory cancer treatments[J]. Semin Cancer Biol, 2018, 52(Pt 2): 228-240.
[6] HANNA G J, O'NEILL A, SHIN K Y, et al. Neoadjuvant and adjuvant nivolumab and lirilumab in patients with recurrent, resectable squamous cell carcinoma of the head and neck[J]. Clin Cancer Res, 2022, 28(3): 468-478.
[7] MACHIELS J P, RENé LEEMANS C, GOLUSINSKI W, et al. Squamous cell carcinoma of the oral cavity, larynx, oropharynx and hypopharynx: EHNS-ESMO-ESTRO Clinical Practice Guidelines for diagnosis, treatment and follow-up[J]. Ann Oncol, 2020, 31(11): 1462-1475.
[8] CRAMER J D, BURTNESS B, LE Q T, et al. The changing therapeutic landscape of head and neck cancer[J]. Nat Rev Clin Oncol, 2019, 16(11): 669-683.
[9] TANG Z M, ZHAO P R, WANG H, et al. Biomedicine meets Fenton chemistry[J]. Chem Rev, 2021, 121(4): 1981-2019.
[10] LIN X H, SONG J B, CHEN X Y, et al. Ultrasound-activated sensitizers and applications[J]. Angew Chem Int Ed, 2020, 59(34): 14212-14233.
[11] XU M M, ZHOU L Q, ZHENG L, et al. Sonodynamic therapy-derived multimodal synergistic cancer therapy[J]. Cancer Lett, 2021, 497: 229-242.
[12] ZHANG Y, ZHANG C F, QIAN W L, et al. Recent advances in MOF-based nanozymes: synthesis, activities, and bioapplications[J]. Biosens Bioelectron, 2024, 263: 116593.
[13] HU Y H, ZHENG Y J, LIU C, et al. Mitochondrial MOF regulates energy metabolism in heart failure via ATP5B hyperacetylation[J]. Cell Rep, 2024, 43(10): 114839.
[14] MALEKI A, SEYEDHAMZEH M, YUAN M, et al. Titanium-based nanoarchitectures for sonodynamic therapy-involved multimodal treatments[J]. Small, 2023, 19(12): e2206253.
[15] XIE X X, ZHANG J X, WANG Y, et al. Nanomaterials augmented bioeffects of ultrasound in cancer immunotherapy[J]. Mater Today Bio, 2023, 24: 100926.
[16] ZHANG N S, ZENG W L, XU Y X, et al. Pyroptosis induction with nanosonosensitizer-augmented sonodynamic therapy combined with PD-L1 blockade boosts efficacy against liver cancer[J]. Adv Healthc Mater, 2024, 13(7): e2302606.
[17] JIANG H, YANG K W, ZHAO X X, et al. Highly stable Zr(IV)-based metal-organic frameworks for chiral separation in reversed-phase liquid chromatography[J]. J Am Chem Soc, 2021, 143(1): 390-398.
[18] PARK J, JIANG Q, FENG D W, et al. Size-controlled synthesis of porphyrinic metal-organic framework and functionalization for targeted photodynamic therapy[J]. J Am Chem Soc, 2016, 138(10): 3518-3525.
[19] LáZARO I A, WELLS C J R, FORGAN R S. Multivariate modulation of the Zr MOF UiO-66 for defect-controlled combination anticancer drug delivery[J]. Angew Chem Int Ed, 2020, 59(13): 5211-5217.
[20] HAO F, YAN Z Y, YAN X P. Intracellular fate and immune response of porphyrin-based nano-sized metal-organic frameworks[J]. Chemosphere, 2022, 307: 135680.
[21] SNETKOV P, ZAKHAROVA K, MOROZKINA S, et al. Hyaluronic acid: the influence of molecular weight on structural, physical, physico-chemical, and degradable properties of biopolymer[J]. Polymers (Basel), 2020, 12(8): 1800.
[22] GHOSH B, BISWAS S. Polymeric micelles in cancer therapy: state of the art[J]. J Control Release, 2021, 332: 127-147.
[23] KYU SHIM M, YANG S, SUN I C, et al. Tumor-activated carrier-free prodrug nanoparticles for targeted cancer Immunotherapy: preclinical evidence for safe and effective drug delivery[J]. Adv Drug Deliv Rev, 2022, 183: 114177.
[24] LIU Y T, SUN Z J. Turning cold tumors into hot tumors by improving T-cell infiltration[J]. Theranostics, 2021, 11(11): 5365-5386.
[25] LIU C P, WANG Y C, LI L M, et al. Engineered extracellular vesicles and their mimetics for cancer immunotherapy[J]. J Control Release, 2022, 349: 679-698.
[26] HIAM-GALVEZ K J, ALLEN B M, SPITZER M H. Systemic immunity in cancer[J]. Nat Rev Cancer, 2021, 21(6): 345-359.
[27] HUANG Z C, LIU L P, ZHU Z Y, et al. Tuning surface valences of nanoengagers to enhance their structural advantages for efficiently redirecting T cells against solid tumors[J]. ACS Nano, 2025, 19(1): 381-395.
[28] MIN H, WANG J, QI Y Q, et al. Biomimetic metal-organic framework nanoparticles for cooperative combination of antiangiogenesis and photodynamic therapy for enhanced efficacy[J]. Adv Mater, 2019, 31(15): e1808200.
[29] WANG Y F, SHI J Q, XIN M H, et al. Cell-drug conjugates[J]. Nat Biomed Eng, 2024, 8(11): 1347-1365.
[30] GAO H B, SUN L, WANG H, et al. In situ non-canonical activation and sensitization of cGAS-STING pathway with manganese telluride nanosheets[J]. Biomaterials, 2025, 318: 123170.
[31] SUN Z H, LIU J, LI Y Y, et al. Aggregation-induced-emission photosensitizer-loaded nano-superartificial dendritic cells with directly presenting tumor antigens and reversed immunosuppression for photodynamically boosted immunotherapy[J]. Adv Mater, 2023, 35(3): e2208555.
Options
文章导航

/

〈 〉