Department of General, Visceral and Transplant Surgery, RWTH Aachen University Hospital, Aachen, Germany.
Institute of Applied Medical Engineering, Helmholtz Institute Aachen, RWTH Aachen University Hospital, Aachen, Germany.
Int J Nanomedicine. 2021 Apr 23;16:2965-2981. doi: 10.2147/IJN.S288379. eCollection 2021.
Pancreatic ductal adenocarcinoma (PDAC) is a cancer with a meager prognosis due to its chemotherapy resistance. A new treatment method may be magnetic fluid hyperthermia (MFH). Magnetoliposomes (ML), consisting of superparamagnetic iron oxide nanoparticles (SPION) stabilized with a phospholipid-bilayer, are exposed to an alternating magnetic field (AMF) to generate heat. To optimize this therapy, we investigated the effects of MFH on human PDAC cell lines and 3D organoid cultures.
ML cytotoxicity was tested on Mia PaCa-2 and PANC-1 cells and on PDAC 3D organoid cultures, generated from resected tissue of patients. The MFH was achieved by AMF application with an amplitude of 40-47 kA/m and a frequency of 270 kHz. The MFH effect on the cell viability of the cell lines and the organoid cultures was investigated at two different time points. Clonogenic assays evaluated the impairment of colony formation. Altering ML set-ups addressed differences arising from intra- vs extracellular ML locations.
Mia PaCa-2 and PANC-1 cells showed no cytotoxic effects at ML concentrations up to 300 µg(Fe)/mL and 225 µg(Fe)/mL, respectively. ML at a concentration of 225 µg(Fe)/mL were also non-toxic for PDAC organoid cultures. MFH treatment using exclusively extracellular ML presented the highest impact on cell viability. Clonogenic assays demonstrated remarkable impairment as long-term outcome in MFH-treated PDAC cell lines. Additionally, we successfully treated PDAC organoids with extracellular ML-derived MFH, resulting in notably reduced cell viabilities 2h and 24 h post treatment. Still, PDAC organoids seem to partly recover from MFH after 24 h as opposed to conventional 2D-cultures.
Treatment with MFH strongly diminished pancreatic cancer cell viability in vitro, making it a promising treatment strategy. As organoids resemble the more advanced in vivo conditions better than conventional 2D cell lines, our organoid model holds great potential for further investigations.
胰腺导管腺癌（PDAC）是一种预后较差的癌症，因为其对化疗有耐药性。一种新的治疗方法可能是磁流体热疗（MFH）。磁载脂质体（ML）由超顺磁性氧化铁纳米粒子（SPION）稳定的磷脂双层组成，在交变磁场（AMF）中产生热量。为了优化这种治疗方法，我们研究了 MFH 对人 PDAC 细胞系和 3D 类器官培养物的影响。
在 Mia PaCa-2 和 PANC-1 细胞以及从患者切除组织生成的 PDAC 3D 类器官培养物上测试 ML 的细胞毒性。MFH 通过应用振幅为 40-47 kA/m、频率为 270 kHz 的 AMF 来实现。在两个不同的时间点研究了 MFH 对细胞系和类器官培养物中细胞活力的影响。克隆形成实验评估了集落形成的损伤。改变 ML 设置解决了细胞内和细胞外 ML 位置差异引起的问题。
Mia PaCa-2 和 PANC-1 细胞在高达 300 µg(Fe)/mL 和 225 µg(Fe)/mL 的 ML 浓度下没有显示出细胞毒性作用。浓度为 225 µg(Fe)/mL 的 ML 对 PDAC 类器官培养物也没有毒性。仅使用细胞外 ML 的 MFH 处理对细胞活力的影响最大。克隆形成实验表明，MFH 治疗后的 PDAC 细胞系作为长期结果具有显著的损伤。此外，我们成功地用细胞外 ML 衍生的 MFH 治疗 PDAC 类器官，导致处理后 2 小时和 24 小时细胞活力明显降低。尽管如此，PDAC 类器官似乎在 24 小时后从 MFH 中部分恢复，而不是传统的 2D 培养物。
MFH 处理强烈降低了体外胰腺癌细胞活力，使其成为一种有前途的治疗策略。由于类器官比传统的 2D 细胞系更能模拟更先进的体内条件，因此我们的类器官模型具有进一步研究的巨大潜力。
