微球和纳米颗粒在经动脉化疗栓塞治疗肝细胞癌中的应用

张楚悦; 史家宁; 王明达; 吴寒; 史立军; 杨田

doi:10.12449/JCH240428

微球和纳米颗粒在经动脉化疗栓塞治疗肝细胞癌中的应用

DOI: 10.12449/JCH240428

张楚悦¹,
史家宁²,
王明达³,
吴寒³,
史立军¹,
杨田^3, , ,

1.
哈尔滨医科大学附属第一医院消化内科，哈尔滨 150007
2.
同济大学医学院附属上海东方医院内镜中心，上海 200120
3.
中国人民解放军海军军医大学第三附属医院肝胆外科，上海 200438

基金项目:

国家自然科学基金 (82273074)

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：张楚悦、史家宁负责撰写论文；吴寒、王明达、杨田负责修改论文；史立军、杨田负责拟定写作思路，指导撰写文章并最后定稿。张楚悦、史家宁对文本贡献等同，同为第一作者。

详细信息

通信作者:
杨田， yangtian6666@hotmail.com （ORCID： 0000-0003-1544-0976）

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出版历程
- 收稿日期: 2023-07-25
- 录用日期: 2023-08-10
- 出版日期: 2024-04-25

Advances in the application of microspheres and nanoparticles in transcatheter arterial chemoembolization for the treatment of hepatocellular carcinoma

1.
Department of Gastroenterology，The First Affiliated Hospital of Harbin Medical University，Harbin 150007，China
2.
Endoscopy Center，Shanghai East Hospital，Tongji University School of Medicine，Shanghai 200120，China
3.
Department of Hepatobiliary Surgery，The Third Affiliated Hospital of Navy Medical University，Shanghai 200438，China

Research funding:

National Natural Science Foundation of China (82273074)

More Information

Corresponding author: YANG Tian， yangtian6666@hotmail.com （ORCID： 0000-0003-1544-0976）

摘要

摘要: 近年来，经动脉化疗栓塞（TACE）是治疗肝细胞癌（HCC）的常用方法。然而，随着栓塞剂技术的不断发展，微球和纳米颗粒方面的新进展为提高TACE的治疗效果和安全性带来了新的希望。本文综述了微球和纳米颗粒在HCC行TACE中的最新进展和应用。首先，介绍了TACE作为治疗手段的背景，以及微球和纳米颗粒技术的兴起。接着，叙述了TACE中不同类型的微球和纳米颗粒的使用情况，并探讨了理想栓塞剂的特性。文章着重描述了在材料科学和工程领域的进展，以及药物释放微球和纳米颗粒与传统TACE在临床效果方面的对比。另外，对影像学在TACE手术中的重要性进行了讨论，并总结了放射性和磁共振可见的栓塞剂的研究进展。文章从多个角度讨论了TACE治疗的未来发展方向和面临的挑战。指出了微球和纳米颗粒与其他治疗方法结合、个性化和精准医学在TACE中的应用，以及TACE在临床转化应用中的潜在方案。同时，提出了伦理和监管方面的问题需要加以探讨。认为先进微球和纳米颗粒在TACE中具有潜在影响，为HCC治疗模式的创新以及通过TACE改善患者预后提供了理论基础和技术支持。
- 微球 /
- 纳米球 /
- 癌，肝细胞 /
- 化学栓塞，治疗性
Abstract: In recent years， transcatheter arterial chemoembolization （TACE） has emerged as a common treatment modality for the treatment of hepatocellular carcinoma （HCC）. However， with the ongoing development of embolic agent techniques， the new advances in microspheres and nanoparticles have brought new hope for improving the efficacy and safety of TACE. This article reviews the latest advances and applications of microspheres and nanoparticles in TACE for HCC. First， this article introduces the background of TACE as a therapeutic approach and the emergence of microsphere and nanoparticle techniques， and then it describes the application of various types of microspheres and nanoparticles in TACE and discusses the requisite attributes of an ideal embolic agents. The article focuses on the advances in material science and engineering， as well as the clinical efficacy of drug-eluting microspheres and nanoparticles versus conventional TACE. Furthermore， it discusses the importance of radiological examination in TACE and summarizes the research advances in the radiopaque and magnetic resonance-visible embolic agents. This article also explores the future development directions and challenges of TACE. It also points out the combination of microspheres and nanoparticles with other treatment modalities， the application of personalized and precision medicine in TACE， and the potential regimen of TACE in clinical translation， and meanwhile， it raises the issues of ethics and regulation that need to be further discussed. It is believed that microspheres and nanoparticles have a potential effect in TACE， which provides a theoretical basis and technical support for innovating HCC treatment regimens and improving the prognosis of patients through TACE interventions.
- Microspheres /
- Nanospheres /
- Carcinoma， Hepatocellular /
- Chemoembolization， Therapeutic

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据估计，长期暴露于甲氨蝶呤(MTX)导致严重肝纤维化的风险约为5%，这促使人们采取强化监测策略。然而，现有证据来源于回顾性研究，这些研究低估了肝病的风险因素。在Atallah等一项纵向队列研究中，使用两种非侵入性标志物评估了长期MTX治疗对肝纤维化的风险。

在2014年—2021年，笔者从6个英国研究中心前瞻性招募了诊断为≥2年类风湿关节炎或银屑病的成年患者。MTX组包括接受MTX治疗≥6个月的患者，而未暴露组包括从未接受MTX的患者。所有的患者都进行了完整的肝脏分析，包括瞬时弹性成像(TE)和增强肝纤维化(ELF)标志物测量。

共纳入999例患者，平均(60.8±12)岁，女性占62.3%。在976例有效TE值中，149例(15.3%)患者肝硬度≥7.9 kPa。在892例有效ELF值中，262例(29.4%)患者ELF≥9.8。年龄和BMI与肝硬度升高和肝纤维化独立相关。MTX累积剂量和持续时间都与肝硬度升高无关。糖尿病是与肝硬度≥7.9 kPa相关性最显著的危险因素(校正比值比=3.19，95%可信区间：1.95~5.20，P＜0.001)。定期使用非甾体类抗炎药与ELF≥9.8的相关性最强(优势比=1.76，95%可信区间：1.20~2.56，P=0.003)，表明类风湿性关节炎的关节炎症程度可能与作为肝纤维化的非侵入性标志物的ELF相混淆。

笔者认为，先前可能高估了MTX本身导致的肝纤维化风险，有必要考虑修改MTX目前的监测准则。

摘译自ATALLAH E, GROVE JI, CROOKS C, et al. Risk of liver fibrosis associated with long-term methotrexate therapy may be overestimated[J]. J Hepatol, 2023. DOI: 10.1016/j.jhep.2022.12.034. [Oline ahead of print]

(吉林大学第一医院肝胆胰内科纪竹慧辛桂杰报道)

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