Shah Rohan M, Rajasekaran Dhivya, Ludford-Menting Mandy, Eldridge Daniel S, Palombo Enzo A, Harding Ian H
Department of Chemistry and Biotechnology, Faculty of Science, Engineering and Technology, Swinburne University of Technology, Hawthorn, Melbourne, Australia.
Immune Signalling Laboratory, Peter MacCallum Cancer Centre, East Melbourne, Australia; Cell Biology Laboratory, Center for Micro-Photonics, Faculty of Science, Engineering and Technology, Swinburne University of Technology Melbourne, Australia.
Colloids Surf B Biointerfaces. 2016 Apr 1;140:204-212. doi: 10.1016/j.colsurfb.2015.12.029. Epub 2015 Dec 28.
Development of drug delivery systems, as much as the drug molecule itself, is an important consideration for improving drug absorption and bioavailability. The mechanisms by which drug carriers enter target cells can differ depending on their size, surface properties and components. Solid lipid nanoparticles (SLNs) have gained an increased attention in recent years and are the drug carriers of interest in this paper. They are known to breach the cell-membrane barrier and have been actively sought to transport biomolecules. Previous studies by our group, and also other groups, provided an extensive characterization of SLNs. However, few studies have investigated the uptake of SLNs and these have had limited mechanistic focus. The aim of this work was to investigate the pathway of uptake of SLNs by human epithelial cells i.e., lung A549 and cervical HeLa cells. To the best of our knowledge, this is first study that investigates the cellular uptake of SLNs by human epithelial cells. The mechanism of cellular uptake was deciphered using pharmacologic inhibitors (sucrose, potassium-free buffer, filipin and cytochalasin B). Imaging techniques and flow assisted cell sorting (FACS) were used to assess the cellular uptake of SLNs loaded with rhodamine 123 as a fluorescent probe. This study provided evidence that the cellular uptake of SLNs was energy-dependent, and the endocytosis of SLNs was mainly dependent on clathrin-mediated mechanisms. The establishment of entry mechanism of SLNs is of fundamental importance for future facilitation of SLNs as biological or drug carriers.
与药物分子本身一样，药物递送系统的开发对于提高药物吸收和生物利用度而言是一个重要的考量因素。药物载体进入靶细胞的机制可能因其大小、表面性质和成分的不同而有所差异。固体脂质纳米粒（SLNs）近年来受到了越来越多的关注，是本文所关注的药物载体。已知它们能够突破细胞膜屏障，并一直被积极用于运输生物分子。我们小组以及其他小组之前的研究对SLNs进行了广泛的表征。然而，很少有研究调查SLNs的摄取情况，而且这些研究的机制重点有限。这项工作的目的是研究人上皮细胞即肺A549细胞和宫颈HeLa细胞对SLNs的摄取途径。据我们所知，这是第一项研究人上皮细胞对SLNs细胞摄取情况的研究。使用药理学抑制剂（蔗糖、无钾缓冲液、制霉菌素和细胞松弛素B）来解读细胞摄取的机制。使用成像技术和流式细胞分选（FACS）来评估负载罗丹明123作为荧光探针的SLNs的细胞摄取情况。这项研究提供了证据，表明SLNs的细胞摄取是能量依赖的，并且SLNs的内吞作用主要依赖于网格蛋白介导的机制。确定SLNs的进入机制对于未来将SLNs用作生物或药物载体至关重要。
