School of Engineering & Materials Science, Queen Mary University of London, London, E1 4NS, UK.
Nanoscale. 2015 Jun 7;7(21):9686-93. doi: 10.1039/c5nr01261a.
Despite our increasing knowledge of cell biology and the recognition of an increasing repertoire of druggable intracellular therapeutic targets, there remain a limited number of approaches to deliver bioactive molecules to cells and even fewer that enable targeted delivery. Layer-by-layer (LbL) microcapsules are assembled using alternate layers of oppositely charged molecules and are potential cell delivery vehicles for applications in nanomedicine. There are a wide variety of charged molecules that can be included in the microcapsule structure including metal nanoparticles that introduce physical attributes. Delivery of bioactive molecules to cells with LbL microcapsules has recently been demonstrated, so in this study we explore the delivery of bioactive molecules (luciferase enzyme and plasmid DNA) to cells using biodegradable microcapsules containing a layer of magnetite nanoparticles. Interestingly, significantly improved intracellular luciferase enzyme activity (25 fold) and increased transfection efficiency with plasmid DNA (3.4 fold) was observed with magnetic microcapsules. The use of a neodymium magnet enabled efficient targeting of magnetic microcapsules which further improved the delivery efficiency of the cargoes as a consequence of increased microcapsule concentration at the magnetic site. Microcapsules were well tolerated by cells in these experiments and only displayed signs of toxicity at a capsule : cell ratio of 100 : 1 and with extended exposure. These studies illustrate how multi-functionalization of LbL microcapsules can improve and target delivery of bioactive molecules to cells.
尽管我们对细胞生物学的了解不断增加，并且认识到越来越多可药用的细胞内治疗靶点，但将生物活性分子递送到细胞的方法仍然有限，能够实现靶向递药的方法就更少了。层层（LbL）微胶囊是使用带相反电荷的分子交替层组装而成的，是应用于纳米医学的潜在细胞递药载体。有各种各样的带电荷分子可以包含在微胶囊结构中，包括引入物理属性的金属纳米粒子。最近已经证明了使用 LbL 微胶囊将生物活性分子递送到细胞中，因此在这项研究中，我们使用含有一层磁铁矿纳米粒子的可生物降解微胶囊来探索生物活性分子（荧光素酶和质粒 DNA）向细胞的递药。有趣的是，用磁性微胶囊观察到细胞内荧光素酶活性显著提高（25 倍），质粒 DNA 的转染效率提高（3.4 倍）。使用钕磁铁能够有效地靶向磁性微胶囊，从而由于磁位处微胶囊浓度的增加，进一步提高了货物的递药效率。在这些实验中，微胶囊被细胞很好地耐受，仅在胶囊与细胞比例为 100：1 且暴露时间延长时才显示出毒性迹象。这些研究说明了如何通过 LbL 微胶囊的多功能化来改善和靶向生物活性分子向细胞的递药。
