类器官芯片在纳米药物递送系统研究中的应用及前景

doi:10.11949/0438-1157.20231262

摘要/Abstract

摘要：

类器官是源自人类干细胞、器官特异性祖细胞及分离肿瘤组织的自组装三维多细胞微型器官模型，可在体外重现器官的关键结构特征与生理机能。微流控芯片作为类器官的体外培养平台，为研究细胞在异质群体和微环境中的行为提供机会，因此，成为助力人类器官发育研究、疾病建模及药物筛选的强大工具。基于先进纳米技术构建的药物载体可以显著提升疾病治疗效果，是目前新药物研发和临床治疗的焦点。利用类器官芯片对纳米递送系统的安全性和有效性进行评估，不仅有助于了解药物递送载体与靶点微环境的相互作用机制，科学指导纳米载体的设计；也在患者个性化精准医疗领域具有应用价值。本文讨论了传统二维细胞模型以及动物模型评价纳米药物递送系统的局限性，分析了用类器官芯片作为体外评价平台的优势。在此基础上，总结了近年来类器官芯片在纳米药物递送领域的应用现状与发展方向，并对其前景进行了展望。

关键词: 类器官芯片, 纳米材料, 药物递送, 组织工程学, 细胞生物学

Abstract:

Organoids are self-assembling three-dimensional multicellular structures derived from human stem cells, organ-specific progenitor cells or isolated tumor tissues, which could reproduce the key structural features and physiological functions of organs in vitro. As an in vitro culture platform for organoids, microfluidic chips provide opportunities to study the behavior of cells in heterogeneous populations and microenvironments. Therefore, they have become a powerful tool to assist human organ development research, disease modeling, and drug screening. Nanomaterials, as an advanced carrier for drug delivery, can significantly improve the therapeutic effects of drugs and have become the focus of new drug development. Organoids-on-chip not only provide a reliable platform for evaluating the safety and efficacy of nano-drug delivery systems, but also help the design of nanocarriers and personalized treatment. In this review, we give an update on the limitations of traditional two-dimensional cell models and animal models in nano-drug delivery systems evaluation, with an emphasis on the advantages of in vitro platforms by organoids-on-chip. It also summarized the recent application and development of organoids technology and future directions in nano-drug delivery systems.

Key words: organoids-on-chip, nanomaterials, drug delivery, tissue engineering, cell biology

中图分类号:

Q 813.1⁺3

杨玉维, 李敏, 要智颖, 孙沁林, 刘洋, 葛丹, 孙冰冰. 类器官芯片在纳米药物递送系统研究中的应用及前景[J]. 化工学报, 2024, 75(4): 1209-1221.

Yuwei YANG, Min LI, Zhiying YAO, Qinlin SUN, Yang LIU, Dan GE, Bingbing SUN. Application and prospect of organoids-on-chip in the study of nano-drug delivery systems[J]. CIESC Journal, 2024, 75(4): 1209-1221.

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类别	代表材料	性能	主要应用
聚合物纳米载体^[37-40]	聚乳酸-羟基乙酸共聚物、聚己内酯、聚乙二醇、壳聚糖	聚合物外壳可增加所负载蛋白质和核酸的稳定性，使其免受蛋白酶和核酸酶的降解；可生物降解；生物相容性好	体外激活药物释放、靶向递送、光动力疗法、光热疗法、生物传感、组织成像
脂质体纳米载体^[41-43]	磷脂聚合物纳米胶束、脂质体、固体脂质体纳米颗粒	可以同时包载水溶性药物和脂溶性药物；具有可修饰性；增强药物靶向性；延长药物作用时间、提高药物稳定性	基因递送、光动力疗法、光热疗法、基因疗法、组织工程
水凝胶纳米载体^[44-45]	DNA-水凝胶、光响应型水凝胶、ATP响应型水凝胶	比表面积大；装载效率高；稳定性好；可通过控制水凝胶网格降解、溶胀以及机械变形来实现对药物的控释	刺激响应型药物释放、基因递送、组织工程
无机纳米载体^[46-49]	金纳米颗粒、二氧化硅纳米颗粒、氧化铁纳米颗粒	合成简单；比表面积大；表面易修饰；具有光热和光动力效应；具有良好的荧光特性	荧光生物成像、多光子生物成像、磁引导药物递送、基因治疗

类别	代表材料	性能	主要应用
聚合物纳米载体^[37-40]	聚乳酸-羟基乙酸共聚物、聚己内酯、聚乙二醇、壳聚糖	聚合物外壳可增加所负载蛋白质和核酸的稳定性，使其免受蛋白酶和核酸酶的降解；可生物降解；生物相容性好	体外激活药物释放、靶向递送、光动力疗法、光热疗法、生物传感、组织成像
脂质体纳米载体^[41-43]	磷脂聚合物纳米胶束、脂质体、固体脂质体纳米颗粒	可以同时包载水溶性药物和脂溶性药物；具有可修饰性；增强药物靶向性；延长药物作用时间、提高药物稳定性	基因递送、光动力疗法、光热疗法、基因疗法、组织工程
水凝胶纳米载体^[44-45]	DNA-水凝胶、光响应型水凝胶、ATP响应型水凝胶	比表面积大；装载效率高；稳定性好；可通过控制水凝胶网格降解、溶胀以及机械变形来实现对药物的控释	刺激响应型药物释放、基因递送、组织工程
无机纳米载体^[46-49]	金纳米颗粒、二氧化硅纳米颗粒、氧化铁纳米颗粒	合成简单；比表面积大；表面易修饰；具有光热和光动力效应；具有良好的荧光特性	荧光生物成像、多光子生物成像、磁引导药物递送、基因治疗

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