Cellular Delivery Systems
The small size of nanoparticles and nanocages enables them to overcome various biological barriers and enter target cells, which is an attractive feature for various applications in biomedicine. For example, quantum dots, gold, and magnetic nanoparticles have been used as delivery carriers for small-interference RNA (siRNA), which has been applied for silencing specifi c genes in vitro and in vivo. [1][2][3] Recently, mesoporous silica nanoparticles were proposed as ideal drug-delivery carriers in tumor therapy. [4][5][6] However, undesired cytotoxic effects and cellular responses, triggered by inorganic nanomaterials, remain a major challenge for in vivo applications. [ 7 , 8 ] Upon cellular uptake, interactions of nanoparticles with cellular components, for example, membranes, proteins, and DNA, can signifi cantly contribute to the toxicity. [9][10][11] Moreover, new investigations frequently reveal undesired effects of materials that were once regarded as promising and safe. In 2009, Park et al. demonstrated that porous silica nanoparticles were biodegradable in vivo and excellently biocompatible and a use for in vivo tumor imaging was proposed. [ 12 ] One year later, however, Huang et al. demonstrated that mesoporous silica nanoparticles can promote tumor growth in vivo due to their ability to decrease cellular reactive oxygen species (ROS). [ 13 ] Aside from the generated intracellular toxicity, toxic ion leakage and remote toxicity can also be induced by extracellular inorganic nanocarriers. [ 8 , 14 ] Therefore, it is of great importance to develop a biocompatible carrier system that allows investigations addressing intra-and extracellular toxicity.
Compared with synthetic carriers, biological ones, such as apoferritin, show obvious superiority with regard to biocompatibility. Being the demineralized form of the iron-storage protein ferritin, apoferritin is a globular protein with an outer diameter of 12 nm and an internal cavity of 7.6 nm. Distributed around the sphere, there are 14 small channels, each 3-4 Å in diameter, perforating the protein shell and providing size selectivity for ions or molecules to enter the interior