Department of Rheumatology and Immunology, Institute of Translational Medicine, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210002, China.
State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, China.
Adv Sci (Weinh). 2023 Apr;10(12):e2206004. doi: 10.1002/advs.202206004. Epub 2023 Feb 19.
Chemotherapy is an essential postoperative treatment for pancreatic cancer, while due to the lack of effective drug evaluation platforms, the therapeutic outcomes are hampered by tumor heterogeneity among individuals. Here, a novel microfluidic encapsulated and integrated primary pancreatic cancer cells platform is proposed for biomimetic tumor 3D cultivation and clinical drug evaluation. These primary cells are encapsulated into hydrogel microcapsules of carboxymethyl cellulose cores and alginate shells based on a microfluidic electrospray technique. Benefiting from the good monodispersity, stability, and precise dimensional controllability of the technology, the encapsulated cells can proliferate rapidly and spontaneously form 3D tumor spheroids with highly uniform size and good cell viability. By integrating these encapsulated tumor spheroids into a microfluidic chip with concentration gradient channels and culture chambers, dynamic and high-throughput drug evaluation of different chemotherapy regimens could be realized. It is demonstrated that different patient-derived tumor spheroids show different drug sensitivity on-chip, which is significantly consistent with the clinical follow-up study after the operation. The results demonstrate that the microfluidic encapsulated and integrated tumor spheroids platform has great application potential in clinical drug evaluation.
化疗是胰腺癌术后的重要治疗手段,但由于缺乏有效的药物评价平台,个体间肿瘤异质性阻碍了治疗效果。本研究提出了一种新型的微流控包封集成式原代胰腺癌细胞平台,用于仿生肿瘤 3D 培养和临床药物评价。基于微流控电喷技术,将原代细胞包封在羧甲基纤维素核和海藻酸盐壳的水凝胶微胶囊中。得益于该技术良好的单分散性、稳定性和精确的尺寸可控性,包封的细胞能够快速增殖,并自发形成具有高度均匀大小和良好细胞活力的 3D 肿瘤球体。通过将这些包封的肿瘤球体集成到具有浓度梯度通道和培养室的微流控芯片中,可以实现不同化疗方案的动态高通量药物评价。研究表明,不同患者来源的肿瘤球体在芯片上表现出不同的药物敏感性,与术后临床随访研究结果具有显著的一致性。结果表明,微流控包封集成肿瘤球体平台在临床药物评价中具有巨大的应用潜力。