Centre for Cell Engineering, Glasgow University, Glasgow, UK.
Biomaterials. 2010 May;31(15):4392-400. doi: 10.1016/j.biomaterials.2010.01.096. Epub 2010 Feb 26.
Magnetic nanoparticles are widely used in bioapplications such as imaging (MRI), targeted delivery (drugs/genes) and cell transfection (magnetofection). Historically, the impermeable nature of both the plasma and nuclear membranes hinder potential. Researchers combat this by developing techniques to enhance cellular and nuclear uptake. Two current popular methods are using external magnetic fields to remotely control particle direction or functionalising the nanoparticles with a cell penetrating peptide (e.g. tat); both of which facilitate cell entry. This paper compares the success of both methods in terms of nanoparticle uptake, analysing the type of magnetic forces the particles experience, and determines gross cell response in terms of morphology and structure and changes at the gene level via microarray analysis. Results indicated that both methods enhanced uptake via a caveolin dependent manner, with tat peptide being the more efficient and achieving nuclear uptake. On comparison to control cells, many groups of gene changes were observed in response to the particles. Importantly, the magnetic field also caused many change in gene expression, regardless of the nanoparticles, and appeared to cause F-actin alignment in the cells. Results suggest that static fields should be modelled and analysed prior to application in culture as cells clearly respond appropriately. Furthermore, the use of cell penetrating peptides may prove more beneficial in terms of enhancing uptake and maintaining cell homeostasis than a magnetic field.
磁性纳米粒子在生物应用中被广泛应用，如成像（MRI）、靶向递送（药物/基因）和细胞转染（磁转染）。历史上，等离子体和核膜的不可渗透性质阻碍了其发展。研究人员通过开发增强细胞和核摄取的技术来克服这一难题。目前两种流行的方法是使用外部磁场远程控制粒子方向，或用穿透细胞膜的肽（如 tat）对纳米粒子进行功能化；这两种方法都有利于细胞进入。本文比较了这两种方法在纳米粒子摄取方面的成功，分析了粒子所经历的磁力类型，并通过微阵列分析确定了细胞形态和结构的总体变化以及基因水平的变化。结果表明，这两种方法都通过网格蛋白依赖的方式增强了摄取，tat 肽更有效，并实现了核摄取。与对照细胞相比，观察到许多基因变化组对粒子作出反应。重要的是，无论是否使用纳米粒子，磁场都会导致基因表达的许多变化，并且似乎会导致细胞中的 F-肌动蛋白排列。结果表明，在应用于培养物之前，应该对静磁场进行建模和分析，因为细胞显然会对此作出适当的反应。此外，与磁场相比，穿透细胞膜的肽的使用可能在增强摄取和维持细胞内稳态方面更具优势。
