Chou Ming-Ju, Yu Hsing-Yi, Hsia Jui-Ching, Chen Ying-Hou, Hung Tzu-Ting, Chao Hsiao-Mei, Chern Edward, Huang Yi-You
Institute of Biomedical Engineering, National Taiwan University, Taipei 10617, Taiwan.
niChe Lab for Stem Cell and Regenerative Medicine, Department of Biochemical Science and Technology, National Taiwan University, Taipei 10617, Taiwan.
Materials (Basel). 2018 Feb 15;11(2):301. doi: 10.3390/ma11020301.
Intracellular protein delivery may provide a safe and non-genome integrated strategy for targeting abnormal or specific cells for applications in cell reprogramming therapy. Thus, highly efficient intracellular functional protein delivery would be beneficial for protein drug discovery. In this study, we generated a cationic polyethyleneimine (PEI)-modified gelatin nanoparticle and evaluated its intracellular protein delivery ability in vitro and in vivo. The experimental results showed that the PEI-modified gelatin nanoparticle had a zeta potential of approximately +60 mV and the particle size was approximately 135 nm. The particle was stable at different biological pH values and temperatures and high protein loading efficiency was observed. The fluorescent image results revealed that large numbers of particles were taken up into the mammalian cells and escaped from the endosomes into the cytoplasm. In a mouse C26 cell-xenograft cancer model, particles accumulated in cancer cells. In conclusion, the PEI-modified gelatin particle may provide a biodegradable and highly efficient protein delivery system for use in regenerative medicine and cancer therapy.
细胞内蛋白质递送可为细胞重编程治疗中靶向异常或特定细胞提供一种安全且非基因组整合的策略。因此，高效的细胞内功能性蛋白质递送将有利于蛋白质药物的研发。在本研究中，我们制备了一种阳离子聚乙烯亚胺（PEI）修饰的明胶纳米颗粒，并在体外和体内评估了其细胞内蛋白质递送能力。实验结果表明，PEI修饰的明胶纳米颗粒的zeta电位约为+60 mV，粒径约为135 nm。该颗粒在不同的生物pH值和温度下均稳定，且观察到高蛋白负载效率。荧光图像结果显示，大量颗粒被哺乳动物细胞摄取并从内体逃逸到细胞质中。在小鼠C26细胞异种移植癌模型中，颗粒在癌细胞中积累。总之，PEI修饰的明胶颗粒可为再生医学和癌症治疗提供一种可生物降解且高效的蛋白质递送系统。
