Institute of Applied Medical Engineering, RWTH Aachen University and University Hospital, Aachen, Germany. Physikalisch-Technische Bundesanstalt, Berlin, Germany.
Nanotechnology. 2019 May 3;30(18):184004. doi: 10.1088/1361-6528/ab033e. Epub 2019 Jan 30.
The internalization kinetics resulting from magnetic nanoparticle interactions with tumor cells play an important role in nanoparticle-based cancer treatment efficiency. Here, the uptake kinetics of magnetoliposomes (ML) into human pancreatic tumor cells (MiaPaCa-2 and BxPC-3) are quantified using magnetic particle spectrometry. A comparison to the uptake kinetics for healthy L929 cells is given. The experimental results are used for the development of an uptake kinetics model describing the three relevant internalization processes: ML adsorption to the cell membrane, endo- and exocytosis. By fitting of experimental data, the rate constant of each internalization process is determined enabling the prediction of internalized ML at any incubation time. After seven hours incubation time, MiaPaCa-2 internalized three times more ML than BxPC-3 and L929 cells even though their ML adsorption rate constants were nearly the same. As the interaction of the ML with the cell membrane is non-specific, the uptake kinetics mirror the individual cell response to ML internalization. With a new mathematical term to cover the exocytosis contribution to the overall internalization process, the extended uptake kinetics model offers new possibilities to analyze the specific internalization mechanism for other nanoparticle and cell types.
磁纳米粒子与肿瘤细胞相互作用导致的内化动力学在基于纳米粒子的癌症治疗效率中起着重要作用。在这里,使用磁性粒子谱法定量测定了载脂蛋白体(ML)进入人胰腺肿瘤细胞(MiaPaCa-2 和 BxPC-3)的摄取动力学。并与健康 L929 细胞的摄取动力学进行了比较。实验结果用于开发描述三个相关内化过程的摄取动力学模型:ML 吸附到细胞膜、内吞作用和外排作用。通过拟合实验数据,确定了每个内化过程的速率常数,从而可以预测任何孵育时间内化的 ML。孵育 7 小时后,MiaPaCa-2 内化的 ML 是 BxPC-3 和 L929 细胞的三倍,尽管它们的 ML 吸附速率常数几乎相同。由于 ML 与细胞膜的相互作用是非特异性的,摄取动力学反映了细胞对 ML 内化的个体反应。通过引入一个新的数学术语来涵盖外排作用对整体内化过程的贡献,扩展的摄取动力学模型为分析其他纳米粒子和细胞类型的特定内化机制提供了新的可能性。